what is a research synthesis

How to Synthesize Written Information from Multiple Sources

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When you write a literature review or essay, you have to go beyond just summarizing the articles you’ve read – you need to synthesize the literature to show how it all fits together (and how your own research fits in).

Synthesizing simply means combining. Instead of summarizing the main points of each source in turn, you put together the ideas and findings of multiple sources in order to make an overall point.

At the most basic level, this involves looking for similarities and differences between your sources. Your synthesis should show the reader where the sources overlap and where they diverge.

Unsynthesized Example

Franz (2008) studied undergraduate online students. He looked at 17 females and 18 males and found that none of them liked APA. According to Franz, the evidence suggested that all students are reluctant to learn citations style. Perez (2010) also studies undergraduate students. She looked at 42 females and 50 males and found that males were significantly more inclined to use citation software ( p < .05). Findings suggest that females might graduate sooner. Goldstein (2012) looked at British undergraduates. Among a sample of 50, all females, all confident in their abilities to cite and were eager to write their dissertations.

Synthesized Example

Studies of undergraduate students reveal conflicting conclusions regarding relationships between advanced scholarly study and citation efficacy. Although Franz (2008) found that no participants enjoyed learning citation style, Goldstein (2012) determined in a larger study that all participants watched felt comfortable citing sources, suggesting that variables among participant and control group populations must be examined more closely. Although Perez (2010) expanded on Franz’s original study with a larger, more diverse sample…

Step 1: Organize your sources

After collecting the relevant literature, you’ve got a lot of information to work through, and no clear idea of how it all fits together.

Before you can start writing, you need to organize your notes in a way that allows you to see the relationships between sources.

One way to begin synthesizing the literature is to put your notes into a table. Depending on your topic and the type of literature you’re dealing with, there are a couple of different ways you can organize this.

Summary table

A summary table collates the key points of each source under consistent headings. This is a good approach if your sources tend to have a similar structure – for instance, if they’re all empirical papers.

Each row in the table lists one source, and each column identifies a specific part of the source. You can decide which headings to include based on what’s most relevant to the literature you’re dealing with.

For example, you might include columns for things like aims, methods, variables, population, sample size, and conclusion.

For each study, you briefly summarize each of these aspects. You can also include columns for your own evaluation and analysis.

The summary table gives you a quick overview of the key points of each source. This allows you to group sources by relevant similarities, as well as noticing important differences or contradictions in their findings.

Synthesis matrix

A synthesis matrix is useful when your sources are more varied in their purpose and structure – for example, when you’re dealing with books and essays making various different arguments about a topic.

Each column in the table lists one source. Each row is labeled with a specific concept, topic or theme that recurs across all or most of the sources.

Then, for each source, you summarize the main points or arguments related to the theme.

The purposes of the table is to identify the common points that connect the sources, as well as identifying points where they diverge or disagree.

Step 2: Outline your structure

Now you should have a clear overview of the main connections and differences between the sources you’ve read. Next, you need to decide how you’ll group them together and the order in which you’ll discuss them.

For shorter papers, your outline can just identify the focus of each paragraph; for longer papers, you might want to divide it into sections with headings.

There are a few different approaches you can take to help you structure your synthesis.

If your sources cover a broad time period, and you found patterns in how researchers approached the topic over time, you can organize your discussion chronologically .

That doesn’t mean you just summarize each paper in chronological order; instead, you should group articles into time periods and identify what they have in common, as well as signalling important turning points or developments in the literature.

If the literature covers various different topics, you can organize it thematically .

That means that each paragraph or section focuses on a specific theme and explains how that theme is approached in the literature.

Source Used with Permission: The Chicago School

If you’re drawing on literature from various different fields or they use a wide variety of research methods, you can organize your sources methodologically .

That means grouping together studies based on the type of research they did and discussing the findings that emerged from each method.

If your topic involves a debate between different schools of thought, you can organize it theoretically .

That means comparing the different theories that have been developed and grouping together papers based on the position or perspective they take on the topic, as well as evaluating which arguments are most convincing.

Step 3: Write paragraphs with topic sentences

What sets a synthesis apart from a summary is that it combines various sources. The easiest way to think about this is that each paragraph should discuss a few different sources, and you should be able to condense the overall point of the paragraph into one sentence.

This is called a topic sentence , and it usually appears at the start of the paragraph. The topic sentence signals what the whole paragraph is about; every sentence in the paragraph should be clearly related to it.

A topic sentence can be a simple summary of the paragraph’s content:

“Early research on [x] focused heavily on [y].”

For an effective synthesis, you can use topic sentences to link back to the previous paragraph, highlighting a point of debate or critique:

“Several scholars have pointed out the flaws in this approach.” “While recent research has attempted to address the problem, many of these studies have methodological flaws that limit their validity.”

By using topic sentences, you can ensure that your paragraphs are coherent and clearly show the connections between the articles you are discussing.

As you write your paragraphs, avoid quoting directly from sources: use your own words to explain the commonalities and differences that you found in the literature.

Don’t try to cover every single point from every single source – the key to synthesizing is to extract the most important and relevant information and combine it to give your reader an overall picture of the state of knowledge on your topic.

Step 4: Revise, edit and proofread

Like any other piece of academic writing, synthesizing literature doesn’t happen all in one go – it involves redrafting, revising, editing and proofreading your work.

Checklist for Synthesis

•   Do I introduce the paragraph with a clear, focused topic sentence?
•   Do I discuss more than one source in the paragraph?
•   Do I mention only the most relevant findings, rather than describing every part of the studies?
•   Do I discuss the similarities or differences between the sources, rather than summarizing each source in turn?
•   Do I put the findings or arguments of the sources in my own words?
•   Is the paragraph organized around a single idea?
•   Is the paragraph directly relevant to my research question or topic?
•   Is there a logical transition from this paragraph to the next one?

Further Information

How to Synthesise: a Step-by-Step Approach

Help…I”ve Been Asked to Synthesize!

Learn how to Synthesise (combine information from sources)

How to write a Psychology Essay

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How to Write a Psychology Essay

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• Published: 08 March 2018

Meta-analysis and the science of research synthesis

• Jessica Gurevitch 1 ,
• Julia Koricheva 2 ,
• Shinichi Nakagawa 3 , 4 &
• Gavin Stewart 5  

Nature volume  555 ,  pages 175–182 ( 2018 ) Cite this article

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Meta-analysis is the quantitative, scientific synthesis of research results. Since the term and modern approaches to research synthesis were first introduced in the 1970s, meta-analysis has had a revolutionary effect in many scientific fields, helping to establish evidence-based practice and to resolve seemingly contradictory research outcomes. At the same time, its implementation has engendered criticism and controversy, in some cases general and others specific to particular disciplines. Here we take the opportunity provided by the recent fortieth anniversary of meta-analysis to reflect on the accomplishments, limitations, recent advances and directions for future developments in the field of research synthesis.

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Acknowledgements

We dedicate this Review to the memory of Ingram Olkin and William Shadish, founding members of the Society for Research Synthesis Methodology who made tremendous contributions to the development of meta-analysis and research synthesis and to the supervision of generations of students. We thank L. Lagisz for help in preparing the figures. We are grateful to the Center for Open Science and the Laura and John Arnold Foundation for hosting and funding a workshop, which was the origination of this article. S.N. is supported by Australian Research Council Future Fellowship (FT130100268). J.G. acknowledges funding from the US National Science Foundation (ABI 1262402).

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Department of Ecology and Evolution, Stony Brook University, Stony Brook, 11794-5245, New York, USA

Jessica Gurevitch

School of Biological Sciences, Royal Holloway University of London, Egham, TW20 0EX, Surrey, UK

Julia Koricheva

Evolution and Ecology Research Centre and School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, 2052, New South Wales, Australia

Shinichi Nakagawa

Diabetes and Metabolism Division, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, 2010, New South Wales, Australia

School of Natural and Environmental Sciences, Newcastle University, Newcastle upon Tyne, NE1 7RU, UK

Gavin Stewart

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Gurevitch, J., Koricheva, J., Nakagawa, S. et al. Meta-analysis and the science of research synthesis. Nature 555 , 175–182 (2018). https://doi.org/10.1038/nature25753

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Libraries | Research Guides

Evidence synthesis, how librarians can help, what is evidence synthesis, types of evidence synthesis, which type of review is right for you, statistical support for meta-analysis.

• Evidence Synthesis Resources by Discipline
• Steps in a Review

Attribution

Unless otherwise noted, this guide was adapted from Cornell University's "A Guide to Evidence Synthesis"

At Northwestern University Libraries, we offer general consultations regarding evidence synthesis projects, including literature reviews and systematic reviews. This includes:

• a basic overview of the systematic review process 
• guidance on developing a search strategy and selecting databases
• methods for collecting and organizing articles
• resource recommendations for analyzing results
• identify relevant databases for you to search
• consult on and assist in the development of search strategies
• suggest and instruct on using reference management tools
• suggest tools that can assist in the meta-analysis process
• assist in writing methods section of manuscripts

If the project requires more long-term support, let us know. We may be able to provide additional assistance such as developing and reviewing search strings. Depending on the level of support provided, the researcher may need to provide acknowledgment of the librarian in the final publication.

If you'd like to set up a consultation, complete the Evidence Synthesis Consultation Request form.

Evidence synthesis refers to any method of identifying, selecting, and combining results from multiple studies. Systematic reviews and literature reviews are two methods of identifying and providing summaries of existing literature on a particular topic. They are quite different in scope and practice.

Adapted from Kysh, L. (2013). What’s in a name? The difference between a systematic review and a literature review and why it matters. [Poster] . Retrieved from  http://dx.doi.org/10.6084/m9.figshare.766364 . Licensed under CC-BY. 

Types of evidence synthesis include:

Systematic Review

• Systematically and transparently collect and categorize existing evidence on a broad question of scientific, policy or management importance.
• Compares, evaluates, and synthesizes evidence in a search for the effect of an intervention. 
• Time-intensive and often take months to a year or more to complete. 
• The most commonly referred to type of evidence synthesis. Sometimes confused as a blanket term for other types of reviews.

​​Literature (Narrative) Review

• A broad term referring to reviews with a wide scope and non-standardized methodology. 
• Search strategies, comprehensiveness, and time range covered will vary and do not follow an established protocol.

Scoping Review or Evidence Map

• Seeks to identify research gaps and opportunities for evidence synthesis rather than searching for the effect of an intervention. 
• May critically evaluate existing evidence, but does not attempt to synthesize the results in the way a systematic review would. (see  EE Journal  and  CIFOR )
• May take longer than a systematic review.
• See  Arksey and O'Malley (2005)  for methodological guidance.

​Rapid Review

• Applies Systematic Review methodology within a time-constrained setting.
• Employs methodological "shortcuts" (limiting search terms for example) at the risk of introducing bias.
• Useful for addressing issues needing quick decisions, such as developing policy recommendations.
• See  Evidence Summaries: The Evolution of a Rapid Review Approach

Umbrella Review

• Reviews other systematic reviews on a topic. 
• Often defines a broader question than is typical of a traditional systematic review.
• Most useful when there are competing interventions to consider.

Meta-analysis

• Statistical technique for combining the findings from disparate quantitative studies.
• Uses statistical methods to objectively evaluate, synthesize, and summarize results.
• May be conducted independently or as part of a systematic review.
• Decision Tool What review is right for you? After answering a short series of questions, the tool will generate a suggestion of which type of review will meet you goals.
• Review Methodology Decision Tree (from Cornell University Library) This decision tree can help you decide between a literature review, rapid review, scoping review, systematic review, umbrella review, and a meta-analysis.

The Libraries are not able to provide statistics support for meta-analysis projects. Depending on your affiliation and the extent of your need, the groups linked below may be able to assist with your project:

• Research Computing Services: Consultation and Collaborative Project Support Northwestern's Research Computing Services group offers data consultations and may be able to assist with questions related to statistical programs and languages. They accept consultation requests and will evaluate their ability to assist on a case by case basis.
• Biostatistics Collaboration Center "The mission of the BCC is to support Feinberg School of Medicine investigators in the conduct of high-quality, innovative health-related research by providing expertise in biostatistics, statistical programming, and data management."
• Next: Evidence Synthesis Resources by Discipline >>
• Last Updated: May 9, 2024 9:35 AM
• URL: https://libguides.northwestern.edu/evidencesynthesis

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• Research Guides

How to Write a Literature Review

• 6. Synthesize
• Literature Reviews: A Recap
• Reading Journal Articles
• Does it Describe a Literature Review?
• 1. Identify the Question
• 2. Review Discipline Styles
• Searching Article Databases
• Finding Full-Text of an Article
• Citation Chaining
• When to Stop Searching
• 4. Manage Your References
• 5. Critically Analyze and Evaluate

Synthesis Visualization

Synthesis matrix example.

• 7. Write a Literature Review

• Synthesis Worksheet

About Synthesis

Approaches to synthesis.

You can sort the literature in various ways, for example:

How to Begin?

Read your sources carefully and find the main idea(s) of each source

Look for similarities in your sources – which sources are talking about the same main ideas? (for example, sources that discuss the historical background on your topic)

Use the worksheet (above) or synthesis matrix (below) to get organized

This work can be messy. Don't worry if you have to go through a few iterations of the worksheet or matrix as you work on your lit review!

Four Examples of Student Writing

In the four examples below, only ONE shows a good example of synthesis: the fourth column, or  Student D . For a web accessible version, click the link below the image.

Long description of "Four Examples of Student Writing" for web accessibility

• Download a copy of the "Four Examples of Student Writing" chart

Click on the example to view the pdf.

From Jennifer Lim

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A Guide to Evidence Synthesis: Types of Evidence Synthesis

• Meet Our Team
• Our Published Reviews and Protocols
• What is Evidence Synthesis?

Types of Evidence Synthesis

• Evidence Synthesis Across Disciplines
• Finding and Appraising Existing Systematic Reviews
• 0. Develop a Protocol
• 1. Draft your Research Question
• 2. Select Databases
• 3. Select Grey Literature Sources
• 4. Write a Search Strategy
• 5. Register a Protocol
• 6. Translate Search Strategies
• 7. Citation Management
• 8. Article Screening
• 9. Risk of Bias Assessment
• 10. Data Extraction
• 11. Synthesize, Map, or Describe the Results
• Evidence Synthesis Institute for Librarians
• Open Access Evidence Synthesis Resources

Video: Exploring different review methodologies (3:25 minutes)

Evidence synthesis refers to  any method of identifying, selecting, and combining results from multiple studies . For help selecting a methodology, try our review methodology decision tree. Types of evidence synthesis include: 

​​ Systematic Review

• Systematically and transparently collect and  categorize  existing evidence on a broad question of scientific,  policy or management importance.
• Compares, evaluates, and synthesizes evidence in a search for the effect of an intervention. 
• Time-intensive and often take months to a year or more to complete. 
• The most commonly referred to type of evidence synthesis. Sometimes confused as a blanket term for other types of reviews.

​​ Literature (Narrative) Review

• A broad term referring to reviews with a wide scope and non-standardized methodology. 
• Search strategies, comprehensiveness, and time range covered will vary and do not follow an established protocol.

​ Scoping Review or Evidence Map

• Seeks to identify research gaps and opportunities for evidence synthesis rather than searching for the effect of an intervention. 
• May critically evaluate existing evidence, but does not attempt to synthesize the results in the way a systematic review would. (see  EE Journal  and  CIFOR )
• May take longer than a systematic review.
• See  Arksey and O'Malley (2005)  for methodological guidance.

​ Rapid Review

• Applies Systematic Review methodology within a time-constrained setting.
• Employs methodological "shortcuts" (limiting search terms for example) at the risk of introducing bias.
• Useful for addressing issues needing quick decisions, such as developing policy recommendations.
• See  Evidence Summaries: The Evolution of a Rapid Review Approach

Umbrella Review

• Reviews other systematic reviews on a topic. 
• Often defines a broader question than is typical of a traditional systematic review.
• Most useful when there are competing interventions to consider.

Meta-analysis

• Statistical technique for combining the findings from disparate quantitative studies.
• Uses statistical methods to objectively evaluate, synthesize, and summarize results.
• May be conducted independently or as part of a systematic review.
• << Previous: What is Evidence Synthesis?
• Next: Evidence Synthesis Across Disciplines >>
• Last Updated: May 24, 2024 3:21 PM
• URL: https://guides.library.cornell.edu/evidence-synthesis

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Synthesizing Research

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When combining another author’s ideas with your own, we have talked about how using the can help make sure your points are being adequately argued (if you have not read our handout on the  evidence cycle,  check it out!). Synthesis takes assertions (statements that describe your claim), evidence (facts and proof from outside sources), and commentary (your connections to why the evidence supports your claim), and blends these processes together to make a cohesive paragraph.

In other words, synthesis encompasses several aspects:

• It is the process of integrating support from more than one source for one idea/argument while also identifying how sources are related to each other and to your main idea.
• It is an acknowledgment of how the source material from several sources address the same question/research topic.
• It is the identification of how important factors (assumptions, interpretations of results, theories, hypothesis, speculations, etc.) relate between separate sources.

TIP: It’s a fruit smoothie!

Think of synthesis as a fruit smoothie that you are creating in your paper. You will have unique parts and flavors in your writing that you will need to blend together to make one tasty, unified drink!

Why Synthesis is Important

• Synthesis integrates information from multiple sources, which shows that you have done the necessary research to engage with a topic more fully.
• Research involves incorporating many sources to understand and/or answer a research question, and discovering these connections between the sources helps you better analyze and understand the conversations surrounding your topic.
• Successful synthesis creates links between your ideas helping your paper “flow” and connect better.
• Synthesis prevents your papers from looking like a list of copied and pasted sources from various authors.
• Synthesis is a higher order process in writing—this is the area where you as a writer get to shine and show your audience your reasoning.

Types of Synthesis

Demonstrates how two or more sources agree with one another.

The collaborative nature of writing tutorials has been discussed by scholars like Andrea Lunsford (1991) and Stephen North (1984). In these essays, they explore the usefulness and the complexities of collaboration between tutors and students in writing center contexts.

Demonstrates how two or more sources support a main point in different ways.

While some scholars like Berlin (1987) have primarily placed their focus on the histories of large, famous universities, other scholars like Yahner and Murdick (1991) have found value in connecting their local histories to contrast or highlight trends found in bigger-name universities.

Accumulation

Demonstrates how one source builds on the idea of another.

Although North’s (1984) essay is fundamental to many writing centers today, Lunsford (1991) takes his ideas a step further by identifying different writing center models and also expanding North’s ideas on how writing centers can help students become better writers.

Demonstrates how one source discusses the effects of another source’s ideas.

While Healy (2001) notes the concerns of having primarily email appointments in writing centers, he also notes that constraints like funding, resources, and time affect how online resources are formed. For writing centers, email is the most economical and practical option for those wanting to offer online services but cannot dedicate the time or money to other online tutoring methods. As a result, in Neaderheiser and Wolfe’s (2009) reveals that of all the online options available in higher education, over 91% of institutions utilize online tutoring through email, meaning these constraints significantly affect the types of services writing centers offer.

Discussing Specific Source Ideas/Arguments

To debate with clarity and precision, you may need to incorporate a quote into your statement. Using can help you to thoroughly introduce your quotes so that they fit in to your paragraph and your argument. Remember that you need to use the to bridge between your ideas and outside source material.

Berlin, J. (1987).  Rhetoric and reality: Writing instruction in American colleges, 1900-1985 . Carbondale: Southern Illinois University Press.

Boquet, E.H. (2001). “Our little secret”: A history of writing centers, pre- to open admissions. In R.W. Barnett & J.S. Blumner (Eds.),  The Allyn and Bacon guide to writing center theory and practice  (pp. 42-60). Boston: Allyn and Bacon.

Carino, P. (1995). Early writing centers: Toward a history.  The Writing Center Journal ,  15 (2), 103-15.

Healy, D. (2001). From place to space: Perceptual and administrative issues in the online writing center. In R.W. Barnett & J.S. Blumner (Eds.), T he Allyn and Bacon guide to writing center theory and practice  (pp. 541-554). Boston: Allyn and Bacon.

Lunsford, A. (1991). Collaboration, control, and the idea of the writing center.  The Writing Center Journal ,  12 (1), 310-75.

Neaderheiser, S. & Wolfe, J. (2009). Between technological endorsement and resistance: The state of online writing centers.  The Writing Center Journal .  29 (1), 49-75.

North, S. (1984). The idea of a writing center.  College English ,  45 (5), 433-446.

Yahner, W. & Murdick, W. (1991). The evolution of a writing center: 1972-1990.  Writing Center Journal ,  11 (2), 13-28.

Literature Review Basics

• What is a Literature Review?
• Synthesizing Research
• Using Research & Synthesis Tables
• Additional Resources

Synthesis: What is it?

First, let's be perfectly clear about what synthesizing your research isn't :

• - It isn't  just summarizing the material you read
• - It isn't  generating a collection of annotations or comments (like an annotated bibliography)
• - It isn't  compiling a report on every single thing ever written in relation to your topic

When you  synthesize  your research, your job is to help your reader understand the current state of the conversation on your topic, relative to your research question.  That may include doing the following:

• - Selecting and using representative work on the topic
• - Identifying and discussing trends in published data or results
• - Identifying and explaining the impact of common features (study populations, interventions, etc.) that appear frequently in the literature
• - Explaining controversies, disputes, or central issues in the literature that are relevant to your research question
• - Identifying gaps in the literature, where more research is needed
• - Establishing the discussion to which your own research contributes and demonstrating the value of your contribution

Essentially, you're telling your reader where they are (and where you are) in the scholarly conversation about your project.

Synthesis: How do I do it?

Synthesis, step by step.

This is what you need to do  before  you write your review.

• Identify and clearly describe your research question (you may find the Formulating PICOT Questions table at  the Additional Resources tab helpful).
• Collect sources relevant to your research question.
• Organize and describe the sources you've found -- your job is to identify what  types  of sources you've collected (reviews, clinical trials, etc.), identify their  purpose  (what are they measuring, testing, or trying to discover?), determine the  level of evidence  they represent (see the Levels of Evidence table at the Additional Resources tab ), and briefly explain their  major findings . Use a Research Table to document this step.
• Study the information you've put in your Research Table and examine your collected sources, looking for  similarities  and  differences . Pay particular attention to  populations ,   methods  (especially relative to levels of evidence), and  findings .
• Analyze what you learn in (4) using a tool like a Synthesis Table. Your goal is to identify relevant themes, trends, gaps, and issues in the research.  Your literature review will collect the results of this analysis and explain them in relation to your research question.

Analysis tips

• - Sometimes, what you  don't  find in the literature is as important as what you do find -- look for questions that the existing research hasn't answered yet.
• - If any of the sources you've collected refer to or respond to each other, keep an eye on how they're related -- it may provide a clue as to whether or not study results have been successfully replicated.
• - Sorting your collected sources by level of evidence can provide valuable insight into how a particular topic has been covered, and it may help you to identify gaps worth addressing in your own work.
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Methods for the synthesis of qualitative research: a critical review

Elaine barnett-page.

1 Evidence for Policy and Practice Information and Co-ordinating (EPPI-) Centre, Social Science Research Unit, 18 Woburn Square, London WC1H 0NS, UK

James Thomas

Associated data.

In recent years, a growing number of methods for synthesising qualitative research have emerged, particularly in relation to health-related research. There is a need for both researchers and commissioners to be able to distinguish between these methods and to select which method is the most appropriate to their situation.

A number of methodological and conceptual links between these methods were identified and explored, while contrasting epistemological positions explained differences in approaches to issues such as quality assessment and extent of iteration. Methods broadly fall into 'realist' or 'idealist' epistemologies, which partly accounts for these differences.

Methods for qualitative synthesis vary across a range of dimensions. Commissioners of qualitative syntheses might wish to consider the kind of product they want and select their method – or type of method – accordingly.

The range of different methods for synthesising qualitative research has been growing over recent years [ 1 , 2 ], alongside an increasing interest in qualitative synthesis to inform health-related policy and practice [ 3 ]. While the terms 'meta-analysis' (a statistical method to combine the results of primary studies), or sometimes 'narrative synthesis', are frequently used to describe how quantitative research is synthesised, far more terms are used to describe the synthesis of qualitative research. This profusion of terms can mask some of the basic similarities in approach that the different methods share, and also lead to some confusion regarding which method is most appropriate in a given situation. This paper does not argue that the various nomenclatures are unnecessary, but rather seeks to draw together and review the full range of methods of synthesis available to assist future reviewers in selecting a method that is fit for their purpose. It also represents an attempt to guide the reader through some of the varied terminology to spring up around qualitative synthesis. Other helpful reviews of synthesis methods have been undertaken in recent years with slightly different foci to this paper. Two recent studies have focused on describing and critiquing methods for the integration of qualitative research with quantitative [ 4 , 5 ] rather than exclusively examining the detail and rationale of methods for the synthesis of qualitative research. Two other significant pieces of work give practical advice for conducting the synthesis of qualitative research, but do not discuss the full range of methods available [ 6 , 7 ]. We begin our Discussion by outlining each method of synthesis in turn, before comparing and contrasting characteristics of these different methods across a range of dimensions. Readers who are more familiar with the synthesis methods described here may prefer to turn straight to the 'dimensions of difference' analysis in the second part of the Discussion.

Overview of synthesis methods

Meta-ethnography.

In their seminal work of 1988, Noblit and Hare proposed meta-ethnography as an alternative to meta-analysis [ 8 ]. They cited Strike and Posner's [ 9 ] definition of synthesis as an activity in which separate parts are brought together to form a 'whole'; this construction of the whole is essentially characterised by some degree of innovation, so that the result is greater than the sum of its parts. They also borrowed from Turner's theory of social explanation [ 10 ], a key tenet of which was building 'comparative understanding' [[ 8 ], p22] rather than aggregating data.

To Noblit and Hare, synthesis provided an answer to the question of 'how to "put together" written interpretive accounts' [[ 8 ], p7], where mere integration would not be appropriate. Noblit and Hare's early work synthesised research from the field of education.

Three different methods of synthesis are used in meta-ethnography. One involves the 'translation' of concepts from individual studies into one another, thereby evolving overarching concepts or metaphors. Noblit and Hare called this process reciprocal translational analysis (RTA). Refutational synthesis involves exploring and explaining contradictions between individual studies. Lines-of-argument (LOA) synthesis involves building up a picture of the whole (i.e. culture, organisation etc) from studies of its parts. The authors conceptualised this latter approach as a type of grounded theorising.

Britten et al [ 11 ] and Campbell et al [ 12 ] have both conducted evaluations of meta-ethnography and claim to have succeeded, by using this method, in producing theories with greater explanatory power than could be achieved in a narrative literature review. While both these evaluations used small numbers of studies, more recently Pound et al [ 13 ] conducted both an RTA and an LOA synthesis using a much larger number of studies (37) on resisting medicines. These studies demonstrate that meta-ethnography has evolved since Noblit and Hare first introduced it. Campbell et al claim to have applied the method successfully to non-ethnographical studies. Based on their reading of Schutz [ 14 ], Britten et al have developed both second and third order constructs in their synthesis (Noblit and Hare briefly allude to the possibility of a 'second level of synthesis' [[ 8 ], p28] but do not demonstrate or further develop the idea).

In a more recent development, Sandelowski & Barroso [ 15 ] write of adapting RTA by using it to ' integrate findings interpretively, as opposed to comparing them interpretively' (p204). The former would involve looking to see whether the same concept, theory etc exists in different studies; the latter would involve the construction of a bigger picture or theory (i.e. LOA synthesis). They also talk about comparing or integrating imported concepts (e.g. from other disciplines) as well as those evolved 'in vivo'.

Grounded theory

Kearney [ 16 ], Eaves [ 17 ] and Finfgeld [ 18 ] have all adapted grounded theory to formulate a method of synthesis. Key methods and assumptions of grounded theory, as originally formulated and subsequently refined by Glaser and Strauss [ 19 ] and Strauss and Corbin [ 20 , 21 ], include: simultaneous phases of data collection and analysis; an inductive approach to analysis, allowing the theory to emerge from the data; the use of the constant comparison method; the use of theoretical sampling to reach theoretical saturation; and the generation of new theory. Eaves cited grounded theorists Charmaz [ 22 ] and Chesler [ 23 ], as well as Strauss and Corbin [ 20 ], as informing her approach to synthesis.

Glaser and Strauss [ 19 ] foresaw a time when a substantive body of grounded research should be pushed towards a higher, more abstract level. As a piece of methodological work, Eaves undertook her own synthesis of the synthesis methods used by these authors to produce her own clear and explicit guide to synthesis in grounded formal theory. Kearney stated that 'grounded formal theory', as she termed this method of synthesis, 'is suited to study of phenomena involving processes of contextualized understanding and action' [[ 24 ], p180] and, as such, is particularly applicable to nurses' research interests.

As Kearney suggested, the examples examined here were largely dominated by research in nursing. Eaves synthesised studies on care-giving in rural African-American families for elderly stroke survivors; Finfgeld on courage among individuals with long-term health problems; Kearney on women's experiences of domestic violence.

Kearney explicitly chose 'grounded formal theory' because it matches 'like' with 'like': that is, it applies the same methods that have been used to generate the original grounded theories included in the synthesis – produced by constant comparison and theoretical sampling – to generate a higher-level grounded theory. The wish to match 'like' with 'like' is also implicit in Eaves' paper. This distinguishes grounded formal theory from more recent applications of meta-ethnography, which have sought to include qualitative research using diverse methodological approaches [ 12 ].

Thematic Synthesis

Thomas and Harden [ 25 ] have developed an approach to synthesis which they term 'thematic synthesis'. This combines and adapts approaches from both meta-ethnography and grounded theory. The method was developed out of a need to conduct reviews that addressed questions relating to intervention need, appropriateness and acceptability – as well as those relating to effectiveness – without compromising on key principles developed in systematic reviews. They applied thematic synthesis in a review of the barriers to, and facilitators of, healthy eating amongst children.

Free codes of findings are organised into 'descriptive' themes, which are then further interpreted to yield 'analytical' themes. This approach shares characteristics with later adaptations of meta-ethnography, in that the analytical themes are comparable to 'third order interpretations' and that the development of descriptive and analytical themes using coding invoke reciprocal 'translation'. It also shares much with grounded theory, in that the approach is inductive and themes are developed using a 'constant comparison' method. A novel aspect of their approach is the use of computer software to code the results of included studies line-by-line, thus borrowing another technique from methods usually used to analyse primary research.

Textual Narrative Synthesis

Textual narrative synthesis is an approach which arranges studies into more homogenous groups. Lucas et al [ 26 ] comment that it has proved useful in synthesising evidence of different types (qualitative, quantitative, economic etc). Typically, study characteristics, context, quality and findings are reported on according to a standard format and similarities and differences are compared across studies. Structured summaries may also be developed, elaborating on and putting into context the extracted data [ 27 ].

Lucas et al [ 26 ] compared thematic synthesis with textual narrative synthesis. They found that 'thematic synthesis holds most potential for hypothesis generation' whereas textual narrative synthesis is more likely to make transparent heterogeneity between studies (as does meta-ethnography, with refutational synthesis) and issues of quality appraisal. This is possibly because textual narrative synthesis makes clearer the context and characteristics of each study, while the thematic approach organises data according to themes. However, Lucas et al found that textual narrative synthesis is 'less good at identifying commonality' (p2); the authors do not make explicit why this should be, although it may be that organising according to themes, as the thematic approach does, is comparatively more successful in revealing commonality.

Paterson et al [ 28 ] have evolved a multi-faceted approach to synthesis, which they call 'meta-study'. The sociologist Zhao [ 29 ], drawing on Ritzer's work [ 30 ], outlined three components of analysis, which they proposed should be undertaken prior to synthesis. These are meta-data-analysis (the analysis of findings), meta-method (the analysis of methods) and meta-theory (the analysis of theory). Collectively, these three elements of analysis, culminating in synthesis, make up the practice of 'meta-study'. Paterson et al pointed out that the different components of analysis may be conducted concurrently.

Paterson et al argued that primary research is a construction; secondary research is therefore a construction of a construction. There is need for an approach that recognises this, and that also recognises research to be a product of its social, historical and ideological context. Such an approach would be useful in accounting for differences in research findings. For Paterson et al, there is no such thing as 'absolute truth'.

Meta-study was developed to study the experiences of adults living with a chronic illness. Meta-data-analysis was conceived of by Paterson et al in similar terms to Noblit and Hare's meta-ethnography (see above), in that it is essentially interpretive and seeks to reveal similarities and discrepancies among accounts of a particular phenomenon. Meta-method involves the examination of the methodologies of the individual studies under review. Part of the process of meta-method is to consider different aspects of methodology such as sampling, data collection, research design etc, similar to procedures others have called 'critical appraisal' (CASP [ 31 ]). However, Paterson et al take their critique to a deeper level by establishing the underlying assumptions of the methodologies used and the relationship between research outcomes and methods used. Meta-theory involves scrutiny of the philosophical and theoretical assumptions of the included research papers; this includes looking at the wider context in which new theory is generated. Paterson et al described meta-synthesis as a process which creates a new interpretation which accounts for the results of all three elements of analysis. The process of synthesis is iterative and reflexive and the authors were unwilling to oversimplify the process by 'codifying' procedures for bringing all three components of analysis together.

Meta-narrative

Greenhalgh et al [ 32 ]'s meta-narrative approach to synthesis arose out of the need to synthesise evidence to inform complex policy-making questions and was assisted by the formation of a multi-disciplinary team. Their approach to review was informed by Thomas Kuhn's The Structure of Scientific Revolutions [ 33 ], in which he proposed that knowledge is produced within particular paradigms which have their own assumptions about theory, about what is a legitimate object of study, about what are legitimate research questions and about what constitutes a finding. Paradigms also tend to develop through time according to a particular set of stages, central to which is the stage of 'normal science', in which the particular standards of the paradigm are largely unchallenged and seen to be self-evident. As Greenhalgh et al pointed out, Kuhn saw paradigms as largely incommensurable: 'that is, an empirical discovery made using one set of concepts, theories, methods and instruments cannot be satisfactorily explained through a different paradigmatic lens' [[ 32 ], p419].

Greenhalgh et al synthesised research from a wide range of disciplines; their research question related to the diffusion of innovations in health service delivery and organisation. They thus identified a need to synthesise findings from research which contains many different theories arising from many different disciplines and study designs.

Based on Kuhn's work, Greenhalgh et al proposed that, across different paradigms, there were multiple – and potentially mutually contradictory – ways of understanding the concept at the heart of their review, namely the diffusion of innovation. Bearing this in mind, the reviewers deliberately chose to select key papers from a number of different research 'paradigms' or 'traditions', both within and beyond healthcare, guided by their multidisciplinary research team. They took as their unit of analysis the 'unfolding "storyline" of a research tradition over time' [[ 32 ], p417) and sought to understand diffusion of innovation as it was conceptualised in each of these traditions. Key features of each tradition were mapped: historical roots, scope, theoretical basis; research questions asked and methods/instruments used; main empirical findings; historical development of the body of knowledge (how have earlier findings led to later findings); and strengths and limitations of the tradition. The results of this exercise led to maps of 13 'meta-narratives' in total, from which seven key dimensions, or themes, were identified and distilled for the synthesis phase of the review.

Critical Interpretive Synthesis

Dixon-Woods et al [ 34 ] developed their own approach to synthesising multi-disciplinary and multi-method evidence, termed 'critical interpretive synthesis', while researching access to healthcare by vulnerable groups. Critical interpretive synthesis is an adaptation of meta-ethnography, as well as borrowing techniques from grounded theory. The authors stated that they needed to adapt traditional meta-ethnographic methods for synthesis, since these had never been applied to quantitative as well as qualitative data, nor had they been applied to a substantial body of data (in this case, 119 papers).

Dixon-Woods et al presented critical interpretive synthesis as an approach to the whole process of review, rather than to just the synthesis component. It involves an iterative approach to refining the research question and searching and selecting from the literature (using theoretical sampling) and defining and applying codes and categories. It also has a particular approach to appraising quality, using relevance – i.e. likely contribution to theory development – rather than methodological characteristics as a means of determining the 'quality' of individual papers [ 35 ]. The authors also stress, as a defining characteristic, critical interpretive synthesis's critical approach to the literature in terms of deconstructing research traditions or theoretical assumptions as a means of contextualising findings.

Dixon-Woods et al rejected reciprocal translational analysis (RTA) as this produced 'only a summary in terms that have already been used in the literature' [[ 34 ], p5], which was seen as less helpful when dealing with a large and diverse body of literature. Instead, Dixon-Woods et al adopted a lines-of-argument (LOA) synthesis, in which – rejecting the difference between first, second and third order constructs – they instead developed 'synthetic constructs' which were then linked with constructs arising directly from the literature.

The influence of grounded theory can be seen in particular in critical interpretive synthesis's inductive approach to formulating the review question and to developing categories and concepts, rejecting a 'stage' approach to systematic reviewing, and in selecting papers using theoretical sampling. Dixon-Woods et al also claim that critical interpretive synthesis is distinct in its 'explicit orientation towards theory generation' [[ 34 ], p9].

Ecological Triangulation

Jim Banning is the author of 'ecological triangulation' or 'ecological sentence synthesis', applying this method to the evidence for what works for youth with disabilities. He borrows from Webb et al [ 36 ] and Denzin [ 37 ] the concept of triangulation, in which phenomena are studied from a variety of vantage points. His rationale is that building an 'evidence base' of effectiveness requires the synthesis of cumulative, multi-faceted evidence in order to find out 'what intervention works for what kind of outcomes for what kind of persons under what kind of conditions' [[ 38 ], p1].

Ecological triangulation unpicks the mutually interdependent relationships between behaviour, persons and environments. The method requires that, for data extraction and synthesis, 'ecological sentences' are formulated following the pattern: 'With this intervention, these outcomes occur with these population foci and within these grades (ages), with these genders ... and these ethnicities in these settings' [[ 39 ], p1].

Framework Synthesis

Brunton et al [ 40 ] and Oliver et al [ 41 ] have applied a 'framework synthesis' approach in their reviews. Framework synthesis is based on framework analysis, which was outlined by Pope, Ziebland and Mays [ 42 ], and draws upon the work of Ritchie and Spencer [ 43 ] and Miles and Huberman [ 44 ]. Its rationale is that qualitative research produces large amounts of textual data in the form of transcripts, observational fieldnotes etc. The sheer wealth of information poses a challenge for rigorous analysis. Framework synthesis offers a highly structured approach to organising and analysing data (e.g. indexing using numerical codes, rearranging data into charts etc).

Brunton et al applied the approach to a review of children's, young people's and parents' views of walking and cycling; Oliver et al to an analysis of public involvement in health services research. Framework synthesis is distinct from the other methods outlined here in that it utilises an a priori 'framework' – informed by background material and team discussions – to extract and synthesise findings. As such, it is largely a deductive approach although, in addition to topics identified by the framework, new topics may be developed and incorporated as they emerge from the data. The synthetic product can be expressed in the form of a chart for each key dimension identified, which may be used to map the nature and range of the concept under study and find associations between themes and exceptions to these [ 40 ].

'Fledgling' approaches

There are three other approaches to synthesis which have not yet been widely used. One is an approach using content analysis [ 45 , 46 ] in which text is condensed into fewer content-related categories. Another is 'meta-interpretation' [ 47 ], featuring the following: an ideographic rather than pre-determined approach to the development of exclusion criteria; a focus on meaning in context; interpretations as raw data for synthesis (although this feature doesn't distinguish it from other synthesis methods); an iterative approach to the theoretical sampling of studies for synthesis; and a transparent audit trail demonstrating the trustworthiness of the synthesis.

In addition to the synthesis methods discussed above, Sandelowski and Barroso propose a method they call 'qualitative metasummary' [ 15 ]. It is mentioned here as a new and original approach to handling a collection of qualitative studies but is qualitatively different to the other methods described here since it is aggregative; that is, findings are accumulated and summarised rather than 'transformed'. Metasummary is a way of producing a 'map' of the contents of qualitative studies and – according to Sandelowski and Barroso – 'reflect [s] a quantitative logic' [[ 15 ], p151]. The frequency of each finding is determined and the higher the frequency of a particular finding, the greater its validity. The authors even discuss the calculation of 'effect sizes' for qualitative findings. Qualitative metasummaries can be undertaken as an end in themselves or may serve as a basis for a further synthesis.

Dimensions of difference

Having outlined the range of methods identified, we now turn to an examination of how they compare with one another. It is clear that they have come from many different contexts and have different approaches to understanding knowledge, but what do these differences mean in practice? Our framework for this analysis is shown in Additional file 1 : dimensions of difference [ 48 ]. We have examined the epistemology of each of the methods and found that, to some extent, this explains the need for different methods and their various approaches to synthesis.

Epistemology

The first dimension that we will consider is that of the researchers' epistemological assumptions. Spencer et al [ 49 ] outline a range of epistemological positions, which might be organised into a spectrum as follows:

Subjective idealism : there is no shared reality independent of multiple alternative human constructions

Objective idealism : there is a world of collectively shared understandings

Critical realism : knowledge of reality is mediated by our perceptions and beliefs

Scientific realism : it is possible for knowledge to approximate closely an external reality

Naïve realism : reality exists independently of human constructions and can be known directly [ 49 , 45 , 46 ].

Thus, at one end of the spectrum we have a highly constructivist view of knowledge and, at the other, an unproblematized 'direct window onto the world' view.

Nearly all of positions along this spectrum are represented in the range of methodological approaches to synthesis covered in this paper. The originators of meta-narrative synthesis, critical interpretive synthesis and meta-study all articulate what might be termed a 'subjective idealist' approach to knowledge. Paterson et al [ 28 ] state that meta-study shies away from creating 'grand theories' within the health or social sciences and assume that no single objective reality will be found. Primary studies, they argue, are themselves constructions; meta-synthesis, then, 'deals with constructions of constructions' (p7). Greenhalgh et al [ 32 ] also view knowledge as a product of its disciplinary paradigm and use this to explain conflicting findings: again, the authors neither seek, nor expect to find, one final, non-contestable answer to their research question. Critical interpretive synthesis is similar in seeking to place literature within its context, to question its assumptions and to produce a theoretical model of a phenomenon which – because highly interpretive – may not be reproducible by different research teams at alternative points in time [[ 34 ], p11].

Methods used to synthesise grounded theory studies in order to produce a higher level of grounded theory [ 24 ] appear to be informed by 'objective idealism', as does meta-ethnography. Kearney argues for the near-universal applicability of a 'ready-to-wear' theory across contexts and populations. This approach is clearly distinct from one which recognises multiple realities. The emphasis is on examining commonalities amongst, rather than discrepancies between, accounts. This emphasis is similarly apparent in most meta-ethnographies, which are conducted either according to Noblit and Hare's 'reciprocal translational analysis' technique or to their 'lines-of-argument' technique and which seek to provide a 'whole' which has a greater explanatory power. Although Noblit and Hare also propose 'refutational synthesis', in which contradictory findings might be explored, there are few examples of this having been undertaken in practice, and the aim of the method appears to be to explain and explore differences due to context, rather than multiple realities.

Despite an assumption of a reality which is perhaps less contestable than those of meta-narrative synthesis, critical interpretive synthesis and meta-study, both grounded formal theory and meta-ethnography place a great deal of emphasis on the interpretive nature of their methods. This still supposes a degree of constructivism. Although less explicit about how their methods are informed, it seems that both thematic synthesis and framework synthesis – while also involving some interpretation of data – share an even less problematized view of reality and a greater assumption that their synthetic products are reproducible and correspond to a shared reality. This is also implicit in the fact that such products are designed directly to inform policy and practice, a characteristic shared by ecological triangulation. Notably, ecological triangulation, according to Banning, can be either realist or idealist. Banning argues that the interpretation of triangulation can either be one in which multiple viewpoints converge on a point to produce confirming evidence (i.e. one definitive answer to the research question) or an idealist one, in which the complexity of multiple viewpoints is represented. Thus, although ecological triangulation views reality as complex, the approach assumes that it can be approximately knowable (at least when the realist view of ecological triangulation is adopted) and that interventions can and should be modelled according to the products of its syntheses.

While pigeonholing different methods into specific epistemological positions is a problematic process, we do suggest that the contrasting epistemologies of different researchers is one way of explaining why we have – and need – different methods for synthesis.

Variation in terms of the extent of iteration during the review process is another key dimension. All synthesis methods include some iteration but the degree varies. Meta-ethnography, grounded theory and thematic synthesis all include iteration at the synthesis stage; both framework synthesis and critical interpretive synthesis involve iterative literature searching – in the case of critical interpretive synthesis, it is not clear whether iteration occurs during the rest of the review process. Meta-narrative also involves iteration at every stage. Banning does not mention iteration in outlining ecological triangulation and neither do Lucas or Thomas and Harden for thematic narrative synthesis.

It seems that the more idealist the approach, the greater the extent of iteration. This might be because a large degree of iteration does not sit well with a more 'positivist' ideal of procedural objectivity; in particular, the notion that the robustness of the synthetic product depends in part on the reviewers stating up front in a protocol their searching strategies, inclusion/exclusion criteria etc, and being seen not to alter these at a later stage.

Quality assessment

Another dimension along which we can look at different synthesis methods is that of quality assessment. When the approaches to the assessment of the quality of studies retrieved for review are examined, there is again a wide methodological variation. It might be expected that the further towards the 'realism' end of the epistemological spectrum a method of synthesis falls, the greater the emphasis on quality assessment. In fact, this is only partially the case.

Framework synthesis, thematic narrative synthesis and thematic synthesis – methods which might be classified as sharing a 'critical realist' approach – all have highly specified approaches to quality assessment. The review in which framework synthesis was developed applied ten quality criteria: two on quality and reporting of sampling methods, four to the quality of the description of the sample in the study, two to the reliability and validity of the tools used to collect data and one on whether studies used appropriate methods for helping people to express their views. Studies which did not meet a certain number of quality criteria were excluded from contributing to findings. Similarly, in the example review for thematic synthesis, 12 criteria were applied: five related to reporting aims, context, rationale, methods and findings; four relating to reliability and validity; and three relating to the appropriateness of methods for ensuring that findings were rooted in participants' own perspectives. Studies which were deemed to have significant flaws were excluded and sensitivity analyses were used to assess the possible impact of study quality on the review's findings. Thomas and Harden's use of thematic narrative synthesis similarly applied quality criteria and developed criteria additional to those they found in the literature on quality assessment, relating to the extent to which people's views and perspectives had been privileged by researchers. It is worth noting not only that these methods apply quality criteria but that they are explicit about what they are: assessing quality is a key component in the review process for both of these methods. Likewise, Banning – the originator of ecological triangulation – sees quality assessment as important and adapts the Design and Implementation Assessment Device (DIAD) Version 0.3 (a quality assessment tool for quantitative research) for use when appraising qualitative studies [ 50 ]. Again, Banning writes of excluding studies deemed to be of poor quality.

Greenhalgh et al's meta-narrative review [ 32 ] modified a range of existing quality assessment tools to evaluate studies according to validity and robustness of methods; sample size and power; and validity of conclusions. The authors imply, but are not explicit, that this process formed the basis for the exclusion of some studies. Although not quite so clear about quality assessment methods as framework and thematic synthesis, it might be argued that meta-narrative synthesis shows a greater commitment to the concept that research can and should be assessed for quality than either meta-ethnography or grounded formal theory. The originators of meta-ethnography, Noblit and Hare [ 8 ], originally discussed quality in terms of quality of metaphor, while more recent use of this method has used amended versions of CASP (the Critical Appraisal Skills Programme tool, [ 31 ]), yet has only referred to studies being excluded on the basis of lack of relevance or because they weren't 'qualitative' studies [ 8 ]. In grounded theory, quality assessment is only discussed in terms of a 'personal note' being made on the context, quality and usefulness of each study. However, contrary to expectation, meta-narrative synthesis lies at the extreme end of the idealism/realism spectrum – as a subjective idealist approach – while meta-ethnography and grounded theory are classified as objective idealist approaches.

Finally, meta-study and critical interpretive synthesis – two more subjective idealist approaches – look to the content and utility of findings rather than methodology in order to establish quality. While earlier forms of meta-study included only studies which demonstrated 'epistemological soundness', in its most recent form [ 51 ] this method has sought to include all relevant studies, excluding only those deemed not to be 'qualitative' research. Critical interpretive synthesis also conforms to what we might expect of its approach to quality assessment: quality of research is judged as the extent to which it informs theory. The threshold of inclusion is informed by expertise and instinct rather than being articulated a priori.

In terms of quality assessment, it might be important to consider the academic context in which these various methods of synthesis developed. The reason why thematic synthesis, framework synthesis and ecological triangulation have such highly specified approaches to quality assessment may be that each of these was developed for a particular task, i.e. to conduct a multi-method review in which randomised controlled trials (RCTs) were included. The concept of quality assessment in relation to RCTs is much less contested and there is general agreement on criteria against which quality should be judged.

Problematizing the literature

Critical interpretive synthesis, the meta-narrative approach and the meta-theory element of meta-study all share some common ground in that their review and synthesis processes include examining all aspects of the context in which knowledge is produced. In conducting a review on access to healthcare by vulnerable groups, critical interpretive synthesis sought to question 'the ways in which the literature had constructed the problematics of access, the nature of the assumptions on which it drew, and what has influenced its choice of proposed solutions' [[ 34 ], p6]. Although not claiming to have been directly influenced by Greenhalgh et al's meta-narrative approach, Dixon-Woods et al do cite it as sharing similar characteristics in the sense that it critiques the literature it reviews.

Meta-study uses meta-theory to describe and deconstruct the theories that shape a body of research and to assess its quality. One aspect of this process is to examine the historical evolution of each theory and to put it in its socio-political context, which invites direct comparison with meta-narrative synthesis. Greenhalgh et al put a similar emphasis on placing research findings within their social and historical context, often as a means of seeking to explain heterogeneity of findings. In addition, meta-narrative shares with critical interpretive synthesis an iterative approach to searching and selecting from the literature.

Framework synthesis, thematic synthesis, textual narrative synthesis, meta-ethnography and grounded theory do not share the same approach to problematizing the literature as critical interpretive synthesis, meta-study and meta-narrative. In part, this may be explained by the extent to which studies included in the synthesis represented a broad range of approaches or methodologies. This, in turn, may reflect the broadness of the review question and the extent to which the concepts contained within the question are pre-defined within the literature. In the case of both the critical interpretive synthesis and meta-narrative reviews, terminology was elastic and/or the question formed iteratively. Similarly, both reviews placed great emphasis on employing multi-disciplinary research teams. Approaches which do not critique the literature in the same way tend to have more narrowly-focused questions. They also tend to include a more limited range of studies: grounded theory synthesis includes grounded theory studies, meta-ethnography (in its original form, as applied by Noblit and Hare) ethnographies. The thematic synthesis incorporated studies based on only a narrow range of qualitative methodologies (interviews and focus groups) which were informed by a similarly narrow range of epistemological assumptions. It may be that the authors of such syntheses saw no need for including such a critique in their review process.

Similarities and differences between primary studies

Most methods of synthesis are applicable to heterogeneous data (i.e. studies which use contrasting methodologies) apart from early meta-ethnography and synthesis informed by grounded theory. All methods of synthesis state that, at some level, studies are compared; many are not so explicit about how this is done, though some are. Meta-ethnography is one of the most explicit: it describes the act of 'translation' where terms and concepts which have resonance with one another are subsumed into 'higher order constructs'. Grounded theory, as represented by Eaves [ 17 ], is undertaken according to a long list of steps and sub-steps, includes the production of generalizations about concepts/categories, which comes from classifying these categories. In meta-narrative synthesis, comparable studies are grouped together at the appraisal phase of review.

Perhaps more interesting are the ways in which differences between studies are explored. Those methods with a greater emphasis on critical appraisal may tend (although this is not always made explicit) to use differences in method to explain differences in finding. Meta-ethnography proposes 'refutational synthesis' to explain differences, although there are few examples of this in the literature. Some synthesis methods – for example, thematic synthesis – look at other characteristics of the studies under review, whether types of participants and their context vary, and whether this can explain differences in perspective.

All of these methods, then, look within the studies to explain differences. Other methods look beyond the study itself to the context in which it was produced. Critical interpretive synthesis and meta-study look at differences in theory or in socio-economic context. Critical interpretive synthesis, like meta-narrative, also explores epistemological orientation. Meta-narrative is unique in concerning itself with disciplinary paradigm (i.e. the story of the discipline as it progresses). It is also distinctive in that it treats conflicting findings as 'higher order data' [[ 32 ], p420], so that the main emphasis of the synthesis appears to be on examining and explaining contradictions in the literature.

Going 'beyond' the primary studies

Synthesis is sometimes defined as a process resulting in a product, a 'whole', which is more than the sum of its parts. However, the methods reviewed here vary in the extent to which they attempt to 'go beyond' the primary studies and transform the data. Some methods – textual narrative synthesis, ecological triangulation and framework synthesis – focus on describing and summarising their primary data (often in a highly structured and detailed way) and translating the studies into one another. Others – meta-ethnography, grounded theory, thematic synthesis, meta-study, meta-narrative and critical interpretive synthesis – seek to push beyond the original data to a fresh interpretation of the phenomena under review. A key feature of thematic synthesis is its clear differentiation between these two stages.

Different methods have different mechanisms for going beyond the primary studies, although some are more explicit than others about what these entail. Meta-ethnography proposes a 'Line of Argument' (LOA) synthesis in which an interpretation is constructed to both link and explain a set of parts. Critical interpretive synthesis based its synthesis methods on those of meta-ethnography, developing an LOA using what the authors term 'synthetic constructs' (akin to 'third order constructs' in meta-ethnography) to create a 'synthesising argument'. Dixon-Woods et al claim that this is an advance on Britten et al's methods, in that they reject the difference between first, second and third order constructs.

Meta-narrative, as outlined above, focuses on conflicting findings and constructs theories to explain these in terms of differing paradigms. Meta study derives questions from each of its three components to which it subjects the dataset and inductively generates a number of theoretical claims in relation to it. According to Eaves' model of grounded theory [ 17 ], mini-theories are integrated to produce an explanatory framework. In ecological triangulation, the 'axial' codes – or second level codes evolved from the initial deductive open codes – are used to produce Banning's 'ecological sentence' [ 39 ].

The synthetic product

In overviewing and comparing different qualitative synthesis methods, the ultimate question relates to the utility of the synthetic product: what is it for? It is clear that some methods of synthesis – namely, thematic synthesis, textual narrative synthesis, framework synthesis and ecological triangulation – view themselves as producing an output that is directly applicable to policy makers and designers of interventions. The example of framework synthesis examined here (on children's, young people's and parents' views of walking and cycling) involved policy makers and practitioners in directing the focus of the synthesis and used the themes derived from the synthesis to infer what kind of interventions might be most effective in encouraging walking and cycling. Likewise, the products of the thematic synthesis took the form of practical recommendations for interventions (e.g. 'do not promote fruit and vegetables in the same way in the same intervention'). The extent to which policy makers and practitioners are involved in informing either synthesis or recommendation is less clear from the documents published on ecological triangulation, but the aim certainly is to directly inform practice.

The outputs of synthesis methods which have a more constructivist orientation – meta-study, meta-narrative, meta-ethnography, grounded theory, critical interpretive synthesis – tend to look rather different. They are generally more complex and conceptual, sometimes operating on the symbolic or metaphorical level, and requiring a further process of interpretation by policy makers and practitioners in order for them to inform practice. This is not to say, however, that they are not useful for practice, more that they are doing different work. However, it may be that, in the absence of further interpretation, they are more useful for informing other researchers and theoreticians.

Looking across dimensions

After examining the dimensions of difference of our included methods, what picture ultimately emerges? It seems clear that, while similar in some respects, there are genuine differences in approach to the synthesis of what is essentially textual data. To some extent, these differences can be explained by the epistemological assumptions that underpin each method. Our methods split into two broad camps: the idealist and the realist (see Table ​ Table1 1 for a summary). Idealist approaches generally tend to have a more iterative approach to searching (and the review process), have less a priori quality assessment procedures and are more inclined to problematize the literature. Realist approaches are characterised by a more linear approach to searching and review, have clearer and more well-developed approaches to quality assessment, and do not problematize the literature.

Summary table

N.B.: In terms of the above dimensions, it is generally a question of degree rather than of absolute distinctions.

Mapping the relationships between methods

What is interesting is the relationship between these methods of synthesis, the conceptual links between them, and the extent to which the originators cite – or, in some cases, don't cite – one another. Some methods directly build on others – framework synthesis builds on framework analysis, for example, while grounded theory and constant comparative analysis build on grounded theory. Others further develop existing methods – meta-study, critical interpretive synthesis and meta-narrative all adapt aspects of meta-ethnography, while also importing concepts from other theorists (critical interpretive synthesis also adapts grounded theory techniques).

Some methods share a clear conceptual link, without directly citing one another: for example, the analytical themes developed during thematic synthesis are comparable to the third order interpretations of meta-ethnography. The meta-theory aspect of meta-study is echoed in both meta-narrative synthesis and critical interpretive synthesis (see 'Problematizing the literature, above); however, the originators of critical interpretive synthesis only refer to the originators of meta-study in relation to their use of sampling techniques.

While methods for qualitative synthesis have many similarities, there are clear differences in approach between them, many of which can be explained by taking account of a given method's epistemology.

However, within the two broad idealist/realist categories, any differences between methods in terms of outputs appear to be small.

Since many systematic reviews are designed to inform policy and practice, it is important to select a method – or type of method – that will produce the kind of conclusions needed. However, it is acknowledged that this is not always simple or even possible to achieve in practice.

The approaches that result in more easily translatable messages for policy-makers and practitioners may appear to be more attractive than the others; but we do need to take account lessons from the more idealist end of the spectrum, that some perspectives are not universal.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

Both authors made substantial contributions, with EBP taking a lead on writing and JT on the analytical framework. Both authors read and approved the final manuscript.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/1471-2288/9/59/prepub

Supplementary Material

Dimensions of difference . Ranging from subjective idealism through objective idealism and critical realism to scientific realism to naïve realism

Acknowledgements

The authors would like to acknowledge the helpful contributions of the following in commenting on earlier drafts of this paper: David Gough, Sandy Oliver, Angela Harden, Mary Dixon-Woods, Trisha Greenhalgh and Barbara L. Paterson. We would also like to thank the peer reviewers: Helen J Smith, Rosaline Barbour and Mark Rodgers for their helpful reviews. The methodological development was supported by the Department of Health (England) and the ESRC through the Methods for Research Synthesis Node of the National Centre for Research Methods (NCRM). An earlier draft of this paper currently appears as a working paper on the National Centre for Research Methods' website http://www.ncrm.ac.uk/ .

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Methods for Research Synthesis: A Cross-Disciplinary Approach

October 3, 2013 workshop.

View  workshop video . Download  final program . View  agenda, download papers, and find journal articles .

Read related articles in Risk Analysis , including the workshop summary and introduction  to the series.*

Description:

Methods for research synthesis, including systematic review, meta-analysis, and expert elicitation, are used in almost every field to combine the results of studies that address similar quantities or phenomena. These methods are often employed when estimating parameter values for policy analysis, such as the toxicity of a substance, the monetary value of risk reductions, or the effectiveness of different interventions. However, researchers often face difficult questions about how to choose among these methods and how to adapt each method to particular problems and available data. If used inappropriately, these approaches may yield misleading conclusions about the relative merits of alternative interventions, leading to undesirable policy outcomes.

This Harvard Center for Risk Analysis workshop is part of an interdisciplinary project to improve the use of these methods in policy analysis. Its goal is to promote evidence-based decision making. Its objectives include:

• Increasing cross-disciplinary communication and collaboration on methodological issues by bringing together experts from diverse fields to address common problems;
• Defining more rigorously the types of problems and data for which different synthesis methods are most appropriate, alone or in combination;
• Developing innovative approaches for addressing specific challenges in applying these methods; and,
• Identifying areas where further cross-disciplinary work will be particularly fruitful

The workshop provides an opportunity for presentation and discussion of invited papers on the application of these methods in diverse contexts. Papers  evaluate, for example, how a particular method should be applied in different contexts, or how different methods should be used for a particular application.

Major funding for this project is provided by the National Science Foundation , with additional support from the Harvard Superfund Research Program Research Translation Core, the Harvard University Center for the Environment , the European Association of Environmental and Resource Economists , Gradient , the Health Effects Institute , the Texas Commission on Environmental Quality , the Society for Risk Analysis Economics and Benefits Analysis Specialty Group , and the U.S. Department of Agriculture Economics Research Service .

* We thank Wiley and the Risk Analysis editors for providing temporary free access to the introduction to the series.

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Synthesizing Sources

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When you look for areas where your sources agree or disagree and try to draw broader conclusions about your topic based on what your sources say, you are engaging in synthesis. Writing a research paper usually requires synthesizing the available sources in order to provide new insight or a different perspective into your particular topic (as opposed to simply restating what each individual source says about your research topic).

Note that synthesizing is not the same as summarizing.  

• A summary restates the information in one or more sources without providing new insight or reaching new conclusions.
• A synthesis draws on multiple sources to reach a broader conclusion.

There are two types of syntheses: explanatory syntheses and argumentative syntheses . Explanatory syntheses seek to bring sources together to explain a perspective and the reasoning behind it. Argumentative syntheses seek to bring sources together to make an argument. Both types of synthesis involve looking for relationships between sources and drawing conclusions.

In order to successfully synthesize your sources, you might begin by grouping your sources by topic and looking for connections. For example, if you were researching the pros and cons of encouraging healthy eating in children, you would want to separate your sources to find which ones agree with each other and which ones disagree.

After you have a good idea of what your sources are saying, you want to construct your body paragraphs in a way that acknowledges different sources and highlights where you can draw new conclusions.

As you continue synthesizing, here are a few points to remember:

• Don’t force a relationship between sources if there isn’t one. Not all of your sources have to complement one another.
• Do your best to highlight the relationships between sources in very clear ways.
• Don’t ignore any outliers in your research. It’s important to take note of every perspective (even those that disagree with your broader conclusions).

Example Syntheses

Below are two examples of synthesis: one where synthesis is NOT utilized well, and one where it is.

Parents are always trying to find ways to encourage healthy eating in their children. Elena Pearl Ben-Joseph, a doctor and writer for KidsHealth , encourages parents to be role models for their children by not dieting or vocalizing concerns about their body image. The first popular diet began in 1863. William Banting named it the “Banting” diet after himself, and it consisted of eating fruits, vegetables, meat, and dry wine. Despite the fact that dieting has been around for over a hundred and fifty years, parents should not diet because it hinders children’s understanding of healthy eating.

In this sample paragraph, the paragraph begins with one idea then drastically shifts to another. Rather than comparing the sources, the author simply describes their content. This leads the paragraph to veer in an different direction at the end, and it prevents the paragraph from expressing any strong arguments or conclusions.

An example of a stronger synthesis can be found below.

Parents are always trying to find ways to encourage healthy eating in their children. Different scientists and educators have different strategies for promoting a well-rounded diet while still encouraging body positivity in children. David R. Just and Joseph Price suggest in their article “Using Incentives to Encourage Healthy Eating in Children” that children are more likely to eat fruits and vegetables if they are given a reward (855-856). Similarly, Elena Pearl Ben-Joseph, a doctor and writer for Kids Health , encourages parents to be role models for their children. She states that “parents who are always dieting or complaining about their bodies may foster these same negative feelings in their kids. Try to keep a positive approach about food” (Ben-Joseph). Martha J. Nepper and Weiwen Chai support Ben-Joseph’s suggestions in their article “Parents’ Barriers and Strategies to Promote Healthy Eating among School-age Children.” Nepper and Chai note, “Parents felt that patience, consistency, educating themselves on proper nutrition, and having more healthy foods available in the home were important strategies when developing healthy eating habits for their children.” By following some of these ideas, parents can help their children develop healthy eating habits while still maintaining body positivity.

In this example, the author puts different sources in conversation with one another. Rather than simply describing the content of the sources in order, the author uses transitions (like "similarly") and makes the relationship between the sources evident.

Synthesis in Research: Home

What is synthesis?

Synthesizing information is the opposite of analyzing information. When you read an article or book, you have to pull out specific concepts from the larger document in order to understand it. This is analyzing.

When you synthesize information, you take specific concepts and consider them together to understand how they compare/contrast and how they relate to one another. Synthesis involves combining multiple elements to create a whole.

In regard to course assignments, the  elements  refer to the outside sources you've gathered to support the ideas you want to present. The  whole  then becomes your conclusion(s) about those sources.

How do I synthesize information?

Note: These steps offer a guideline, but do what works for you best.

• This is where you really decide if you want to read specific materials
• If you have gathered a substantial amount of literature and reading all of it would prove overwhelming, read the abstracts to get a better idea of the content, then select the materials that would best support your assignment
• Describe and analyze the findings and/or the author's main ideas
• What's the author's message?
• What evidence do they use to support their message?
• What does the author want a reader to understand?
• What is the larger impact of the author's message?
• Compare and contrast the main ideas and other pertinent information you found in each source
• Evaluate the quality and significance of these main ideas
• Interpret the main ideas in the context of your research question or assignment topic
• This is the step where your synthesis of the information will lead to logical conclusions about that information
• These conclusions should speak directly to your research question (i.e. your question should have an answer)

I would like to give credit to Aultman Health Sciences Library.  Most of the information used to create this guide is from their English Research libguide .

• Last Updated: Apr 8, 2024 2:29 PM
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Systematic reviews & evidence synthesis methods.

• Schedule a Consultation / Meet our Team
• What is Evidence Synthesis?
• Types of Evidence Synthesis
• Evidence Synthesis Across Disciplines
• Finding and Appraising Existing Systematic Reviews
• 0. Preliminary Searching
• 1. Develop a Protocol
• 2. Draft your Research Question
• 3. Select Databases
• 4. Select Grey Literature Sources
• 5. Write a Search Strategy
• 6. Register a Protocol
• 7. Translate Search Strategies
• 8. Citation Management
• 9. Article Screening
• 10. Risk of Bias Assessment
• 11. Data Extraction
• 12. Synthesize, Map, or Describe the Results
• Open Access Evidence Synthesis Resources

Preliminary Searching

Preliminary search of the literature.

Before beginning any evidence synthesis project, you will need to search the literature in your topic area for 2 purposes:

• To determine if there is enough evidence to support an evidence synthesis review on this topic
• To determine if other teams have recently published or are already working on a similar review, in which case you may want to adjust your research question or pursue a different topic

Medicine and health sciences reviews

Search at least  PubMed and Cochrane Library for published studies and systematic reviews, and PROSPERO , and the JBI Systematic Review Register for registered protocols. Note that PROSPERO only accepts protocols for systematic reviews, rapid reviews, and umbrella reviews, so if you plan to do another type of review, search OSF and the JBI EBP Database instead. If you plan to include qualitative evidence or topics related to nursing and allied health, you should also search CINAHL and any relevant subject-specific databases, such as PsycInfo .

Interdisciplinary reviews or outside health sciences

Search one or more subject-specific databases as well as an interdisciplinary database, such as Scopus or Web of Science . Search OSF for projects and protocol registrations. For social sciences topics, review this list of Campbell Collaboration Title Registrations .

For more context, see also Chapter 2 of Finding What Works in Health Care: Standards for Systematic Reviews: Standards for Initiating a Systematic Review: "Standards for Initiating a Systematic Review."

• << Previous: Steps in a Systematic Review
• Next: 1. Develop a Protocol >>
• Last Updated: May 25, 2024 10:49 AM
• URL: https://guides.lib.uci.edu/evidence-synthesis

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Green Chemistry

Agile synthesis and automated, high-throughput evaluation of diglycolamides for liquid–liquid extraction of rare-earth elements †.

* Corresponding authors

a U.S. DOE Ames National Laboratory, Iowa State University, Ames, Iowa 50011, USA E-mail: [email protected]

b School of Environmental and Ecological Engineering, Purdue University, West Lafayette, IN 47907, USA E-mail: [email protected]

c School of Mechanical Engineering, Purdue University, West Lafayette, IN 47907, USA

Liquid–liquid extraction is one of the most scalable processes to produce rare-earth elements (REEs) from natural and recycled resources. Accelerating the research, development, and deployment (RD&D) of sustainable processes to manufacture REEs requires both facile synthesis of extractive ligands at scale and fast evaluation of process conditions. Here, we establish an integrated RD&D methodology comprised of agile ligand synthesis and automated high-throughput extraction studies. Using diglycolamides (DGAs) as an example, we first developed a method for DGA synthesis (scalable to 200 g) by directly coupling diglycolic acid and secondary amines via the solvent-free melt-amidation reaction. A substrate scope of the melt-amidation synthesis was demonstrated for 9 different DGAs with good yields (85–96%) and purities (88–96%) without any post-reaction workup or purification process. Life cycle assessment shows that our synthesis method outperforms the prior-art pathway in each environmental impact category, especially showing a 67% reduction in global warming potential. Furthermore, we investigate the structure–activity relationship of various alkyl-substituted DGAs using an automated, high-throughput workflow for liquid–liquid extraction, achieving over 180 runs in 48 hours. The acquired data enables the development of a promising flowsheet for separating light and heavy REEs. The integrated RD&D method of agile synthesis and automated, high-throughput extraction studies paves the way for future iterative development of sustainable production of REEs and other critical materials to meet the needs for clean energy transformation.

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Agile synthesis and automated, high-throughput evaluation of diglycolamides for liquid–liquid extraction of rare-earth elements

L. An, Y. Yao, T. B. Hall, F. Zhao and L. Qi, Green Chem. , 2024, Advance Article , DOI: 10.1039/D4GC01146E

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Introduction to Click Chemistry

A "click" away from discovery.

The traditional process of drug discovery based on natural secondary metabolites has often been slow, costly, and labor-intensive. Even with the advent of combinatorial chemistry and high-throughput screening in past decades, the generation of leads is dependent on the reliability of the individual reactions to construct the new molecular framework.

Click Chemistry Mechanism

Click chemistry is a newer approach to the synthesis of drug-like molecules that can accelerate the drug discovery process by utilizing a few practical and reliable reactions.  Sharpless and coworkers  defined what makes a click reaction as one that is wide in scope and easy to perform, uses only readily available reagents, and is insensitive to oxygen and water. In fact, in several instances, water is the ideal reaction solvent, providing the best yields and highest rates. Reaction work-up and purification uses benign solvents and avoids chromatography. 1

Click Chemistry Reaction Processes

• Simple to perform
• Wide in scope
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• Stereospecific
• Adheres to the 12 Principles of Green Chemistry by generating harmless byproducts, removable by nonchromatographic methods

Click Chemistry Reaction Characteristics 1

• Simple reaction conditions
• Readily and easily available starting materials and reagents
• Use of no solvent, a benign solvent (such as water), or one that is easily removed
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Click chemistry involves the use of a modular approach and has important applications in the fields of drug discovery, combinatorial chemistry, target-templated  in situ  chemistry, and DNA research. 1

Continue learning about click chemistry in drug discovery .

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The Carthamus tinctorius L. genome sequence provides insights into synthesis of unsaturated fatty acids

• Yuanyuan Dong 1   na1 ,
• Xiaojie Wang 2   na1 ,
• Naveed Ahmad 1 ,
• Yepeng Sun 1 ,
• Yuanxin Wang 1 ,
• Xiuming Liu 1 ,
• Yang Jing 1 ,
• Linna Du 1 ,
• Xiaowei Li 1 ,
• Nan Wang 1 ,
• Weican Liu 1 ,
• Fawei Wang 1 ,
• Xiaokun Li 2 &
• Haiyan Li 3  

BMC Genomics volume  25 , Article number:  510 ( 2024 ) Cite this article

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Domesticated safflower ( Carthamus tinctorius L.) is a widely cultivated edible oil crop. However, despite its economic importance, the genetic basis underlying key traits such as oil content, resistance to biotic and abiotic stresses, and flowering time remains poorly understood. Here, we present the genome assembly for C. tinctorius variety Jihong01 , which was obtained by integrating Oxford Nanopore Technologies (ONT) and BGI-SEQ500 sequencing results. The assembled genome was 1,061.1 Mb, and consisted of 32,379 protein-coding genes, 97.71% of which were functionally annotated. Safflower had a recent whole genome duplication (WGD) event in evolution history and diverged from sunflower approximately 37.3 million years ago. Through comparative genomic analysis at five seed development stages, we unveiled the pivotal roles of fatty acid desaturase 2 (FAD2) and fatty acid desaturase 6 (FAD6) in linoleic acid (LA) biosynthesis. Similarly, the differential gene expression analysis further reinforced the significance of these genes in regulating LA accumulation. Moreover, our investigation of seed fatty acid composition at different seed developmental stages unveiled the crucial roles of FAD2 and FAD6 in LA biosynthesis. These findings offer important insights into enhancing breeding programs for the improvement of quality traits and provide reference resource for further research on the natural properties of safflower.

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Introduction

Safflower ( Carthamus tinctorius L.) is a diploid (2n = 24) dicot plant in the family Asteraceae (Compositae) [ 1 ]. It is an annual plant that is predominantly self-pollinated. This herbaceous crop is adapted to hot and dry environments due to its deep root system and xerophytic spines. Therefore, it is widely cultivated in arid and semiarid regions [ 2 ]. Safflower is assumed to have been domesticated in the Fertile Cresent region over 4,000 years ago, and it has a long history of cultivation in Asia, the Mediterranean region, Europe, and the Americas [ 3 , 4 , 5 ].

Safflower is mainly grown as an oil crop, it has been cultivated for use as birdseed and as a source of oil for the paint industry [ 6 , 7 ]. In some areas such as Western Europe, safflower is cultivated as a source of Safflor Yellow (SY) that is produced in the floret, and used as a natural dyestuff [ 8 ]. Safflower is valuable as an edible oil crop because it produces a large amount of oil (approx. 25% oil content in seeds). It has relatively higher polyunsaturated/saturated ratios than other edible oil, which is rich in octadecadienoic acid and contains more than 70% LA [ 9 ]. As a type of essential polyunsaturated fatty acid (PUFA), LA is vital in the dietary composition for both humans and animals. As one of the oldest sources of oil for humans worldwide, the main economic traits of cultivated safflower varieties are related to its composition proportion in LA [ 10 , 11 ]. Fatty acids desaturase such as FAD2 play a crucial role in regulating the composition of fatty acids, including LA. These enzymes catalyze the desaturation reactions necessary for the synthesis of unsaturated fatty acids, from saturated or monounsaturated precursors [ 12 ]. Although, it is not a mainstream oilseed crop in today’s world, it has been cultivated widely and distributed across various geographic regions. The species diversity of safflower could also serve as an important resource for genetic breeding.

The genetic diversity and natural variations in safflower have been studied using several molecular and analytical methods in recent decades [ 3 , 13 ]. More recent studies have provided molecular information for safflower including its complete chloroplast genome [ 14 ], full-length transcriptome [ 15 ], and the locations of 2,008,196 single nucleotide polymorphisms, which were identified from recombinant inbred safflower lines [ 16 ]. The results of those studies and others indicated that the genetic architecture and evolution of safflower domestication are complex [ 17 ]. Such complexity has posed challenges to safflower breeding endeavors. In the past, breeding programs have used hybridization to breed new cultivars [ 18 ] and have characterized the safflower germplasm using various molecular markers, including expressed sequence tags, inter simple sequence repeats, single nucleotide polymorphism, and simple sequence repeat markers [ 15 , 19 , 20 , 21 , 22 ]. Genome evolution involves intricate mechanisms such as gene duplication, divergence, and selection, which shape the genetic landscape of organisms over time. Gene duplication, in particular, serves as a significant driver of genome evolution, often leading to the expansion of gene families [ 23 , 24 ]. Therefore, high-quality safflower reference genome and genome evolution research can reveal genetic structure and phylogenetic details, as well as biosynthesis processes of bioactive compounds. The inaugural sequencing of the safflower cultivar Anhui-1 genome employed PacBio Sequel (Pacific Biosciences) in conjunction with the Illumina Hiseq 2500 sequencing platform. The investigation primarily targeted the biosynthetic pathways of hydroxysafflor yellow A and unsaturated fatty acid [ 25 ].

To deepen our understanding of the genetic landscape of safflower, we conducted genome assembly of the Jihong01 safflower cultivar. This particular landrace is extensively cultivated and sourced from western China. It is also used as a main source of breeding novel safflower varieties with improved medicinal properties. In this research, we provide a genome overview of safflower that includes details of genome evolution, gene family expansion, and putative genes for unsaturated fatty acids biosynthesis and their composition. This reference genome will serve as a platform for investigating the genome background, and for identifying important genes to exploit in genetic breeding programs.

Genome sequencing and assembly

Genomic DNA was extracted from leaves of the “ Jihong01 ” safflower variety and sequenced on BGI-SEQ500 and Oxford Nanopore Technologies (ONT) platforms. We obtained 101 Gb short reads and 130 Gb long reads data in total. By a 17-mer frequency statistics, the size of safflower genome was estimated to be 1,061.1 Mb (Figure S1 ). The primary contigs was assembled by NECAT software ( https://github.com/xiaochuanle/NECAT ) with an N50 of 8.6 Mb. The initial assembly was error-corrected by Pilon [ 26 ], and the redundant sequences were removed by HaploMerger2 [ 27 ]. After several steps of polishing, the total length of the final assembly was 1,061.1 Mb which is close to the estimated genome size (Table S1 ). To generate a chromosomal-level assembly of the safflower genome, a high-throughput chromosome conformation capture (Hi-C) library was constructed and produced 51 Gb valid reads (47×). 98.82% of the final assembly was anchored to 12 pseudochromosomes with length ranging from 68.06 Mb to 106.66 Mb. GC content of the final assembly was 38.37%. The completeness of our assembly was evaluated by BUSCO (Benchmarking Universal Single Copy Orthologs) [ 28 ]. In embryophyta_odb9 dataset, 90.3% BUSCO genes was complete, 2.4% fragmented and 7.3% missing in the assembly. Also, we used LTR Assembly Index (LAI) [ 29 ] values to evaluate the quality of non-coding region in the assembly (Fig.  1 ). The LAI score of our assembly was 21.94, suggesting a high-quality safflower genome assembly.

Overview of the Carthamus tinctorius genome. ( a ) Chromosomal pseudomolecules. ( b ) GC content (1 Mb windows). ( c ) Gene density (1 Mb windows). ( d ) TE density (1 Mb windows). ( e ) LAI score (3 Mb windows with 300 Kb sliding step). Inner grey ribbons indicate links of synteny blocks, while colored ribbons highlight the residues of whole genome triplication

Genome annotation

We identified 63.4% of the assembly as repetitive sequences. The proportion is comparatively close to artichoke (58.4%) [ 30 ]but lower than sunflower (74.7%) [ 31 ] and lettuce (74.2%) [ 32 ], which may be the reason why the genome size of lettuce or sunflower is two to three times larger than that of artichoke and safflower [ 33 ]. The most abundant transposable elements (TEs) were long terminal repeat (LTR) retrotransposons, accounting for 54.2% of the assembly. Like most plants, Gypsy (26.9%) and Copia (25.2%) were found to be the two dominant LTR super families. Similarly, insertion time of LTR was estimated at 1.5 Mya based on the sequence divergence of all LTRs, later than artichoke (Figure S2 ). Importantly, the DNA transposons covered 7.1% of the assembly. A total of 32,379 protein-coding genes were predicted using a combination of homology prediction and transcripts supporting. Distributions of gene set parameters showed a consistent trend with other plants (Figure S3 ). The gene set covered 93.9% complete BUSCOs of embryophyte BUSCO groups. A sum of 97.71% of predicted proteins were functionally annotated against public protein databases (InterPro, UniProt and KEGG). Besides protein-coding genes, we also annotated 131 miRNAs, 998 tRNAs, 3,017 rRNAs and 1,408 snRNAs.

Gene family and phylogeny analysis

Phylogenetic tree was reconstructed based on the coding sequences (CDS) of 212 single-copy gene families. Plants of Monocotyledons, Rosidae and Asteridae were separated into respective branches and each species were clustered at the reported evolutionary positions. Noticeably, safflower and sunflower were clustered into one branch in the phylogenetic tree (Fig.  2 a). Divergence time of safflower and sunflower was estimated at approximately 37.3 Mya, after the whole genome duplication event at the basal of Asteraceae family [ 34 ]. For comparative analysis, we chose high-quality proteins of 10 oil plant species including (oil palm: Elaeis guineensis , soybean: Glycine max , sunflower: Helianthus annuus , Jatropha: Jatropha curcas , walnut: Juglans regia , flax; Linum usitatissimum , olive tree: Olea europaea , castor: Ricinus communis , sesame: Sesamum indicum and maize: Zea mays ) together with our predicted proteins. All proteins were clustered into 27,600 gene families by OrthoMCL [ 35 ] pipeline, within which 495 gene families were safflower-specific. Compared to olive tree and sesame, safflower shared more gene families with sunflower (Fig.  2 b), indicating a closer relationship between safflower and sunflower.

Comparative analysis of Carthamus tinctorius with other oil crops. ( a ) Phylogeny, divergence time and gene family expansion/contraction of 11 species. The green numbers are families under size expansion while the red numbers are families under size contraction. The vertical stacked column right is the ortholog genes in 11 species. ( b ) Venn diagram of safflower, sesame, olive tree and sunflower

Furthermore, gene family size changes was evaluated by CAFE software [ 36 ]. As for safflower, 516 gene families demonstrated under size expansion, while 2,126 gene families indicated under size contraction. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was implemented to the expanded gene families. From which, 225 of 2,751 genes were markedly enriched in fatty acids biosynthesis and metabolism pathways, including linoleic acid metabolism (map00591), alpha-linolenic acid metabolism (map00592) and biosynthesis of unsaturated fatty acids (map01040) (Figure S4 ). Expansion of gene families involved in fatty acid metabolism especially in unsaturated fatty acids biosynthesis may result in high oil production in safflower.

WGD in safflower genome

As a member of Compositae family, safflower had a recent whole genome duplication (WGD) event in evolution history (38–50 Mya) (Figure S5 ). We used WGD pipeline [ 37 ] to calculate Ks distribution of paralogs in safflower, sunflower, lettuce, artichoke and coffee tree, respectively (Fig.  3 a). After the γ duplication event in eudicots (peak of coffee tree), safflower had experienced another WGD event, which was also found in artichoke and lettuce (Ks  ∼  0.75-1). Besides, this round of duplication was a triplication event, illustrated by the residues of triplication (Fig. 1 ) and triplicate synteny blocks between coffee tree and safflower. In Compositae, two rounds of WGD events occurred in Heliantheae species, which revealed that several 1:2 synteny blocks between safflower and sunflower were existed (Fig.  3 b).

WGD events in Carthamus tinctorius evolutionary history. ( a ) Histogram of five species paralog Ks distributions. ( b ) Macrosynteny of gene regions among coffee, safflower and sunflower. Grey lines indicate the synteny blocks between each two species. Red lines highlight the 1:3 between coffee and safflower and 1:2 between safflower and sunflower synteny block corresponding relations

Unsaturated fatty acid biosynthesis pathway

We annotated a total of 1,586 genes involved in lipid metabolism in safflower genome. Proteins of 96 genes were functionally enriched in biosynthesis of unsaturated fatty acids pathway (Table S2 ). In plants, fatty acid desaturases (FAD) catalyse the desaturation reactions of fatty acids. Stearoyl-ACP desaturase (SAD) is a soluble FAD in plastids, transforming stearic acid (C18:0) to oleic acid (C18:1). FAD2 and FAD6 catalyse further desaturation from oleic acid to linoleic acid (C18:2). FAD2 is localised in the endoplasmic reticulum (ER) while FAD6 in the plastid’s inner envelope. In a previous study, researchers have demonstrated the isolation of 11 members of FAD2 family in safflower [ 6 ]. In our assembly, 29 copies of FAD2 genes were annotated, as well as 4 SAD genes and 1 FAD6 gene (Table S3 ). The FAD2 genes were amplified by tandem duplication and formed 2 gene clusters located on chromosome 9 and chromosome 11 respectively (Fig.  4 a). Phylogenetic analysis of FAD2 gene family in safflower and other oil crops indicated that FAD2 gene family were significantly expanded in safflower and sunflower. Also, multi-copies of FAD2 genes were found in flax genome [ 38 ] (Fig.  4 b).

FAD2 gene clusters. ( a ) Two FAD2 gene clusters on chromosome 9 and chromosome 11. The line indicates chromosome segment. Brown arrows indicate FAD2 genes. ( b ) Phylogenetic analysis of the FAD2 gene family among 11 species [ 31 , 38 ]. Each circle indicates a FAD2 gene. Different colors represent different species

We also sequenced transcriptome of seed tissue at five development stages after flowering (days after flowering, DAF) (DAF6, DAF12, DAF18, DAF24, DAF30). Each stage was selected with three duplications. The expression patterns of 96 genes likely involved in the biosynthesis of unsaturated fatty acids pathway were analysed using Mfuzz package [ 39 ] (Table S2 ). The upregulation of FAD2 genes observed from DAF18 to DAF24 (Figure S6 , clusters 2 and 7) implying that linoleic acid biosynthesis could be regulated around the fifth or sixth day after flowering. Moreover, the expression pattern of some genes was significantly enhanced at DAF6, however, as the developmental stages progresses, the expression was supressed (Figure S6 , cluster 9). This includes genes related to acyl-CoA oxidase and very-long-chain enoyl-CoA reductase.

Changes in the fatty acid composition and levels during seed developmental stages

Fatty acids are essential for plant growth and development. FAs are synthesized in plastids and to a large extent transported to the endoplasmic reticulum for modification and lipid assembly. Many genes participate in lipid metabolism within the plastid and endoplasmic reticulum, particularly in fatty acid elongation and desaturation (Fig.  5 a). Fatty acid composition and contents are the most important indicators to measure the lipid quality. We examined the fatty acid composition of seed storage lipids in developing seeds. The contents of fatty acids of seeds in five developmental stages was measured by GC-MS. Compositional analyses of seed oil revealed that palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1) and linoleic acid (C18:2) accounted for a predominant proportion of the lipid content in safflower (Fig.  5 b). The contents of oleic acid (C18:1) and linoleic acid (C18:2) were found the highest at maturity stage. For instance, C18:1n7, C18:1n9 and C18:2n6 reached 1,776, 1,666, 1,510 µg/g DW, increased by 29.9, 5.4, and 2.6 times when compared to the early stages of grain formation, respectively. According to the data results, C18:3n3 and C18:3n6 did not belong to the high content of PUFA, and their contents decreased first and then increased in the seed developmental stage. In addition to this, most of the fatty acids were increased in the seeds except C14:1, which was decreased. The composition and content of fatty acids in safflower seeds during seed development indicated that the synthesis and accumulation of polyunsaturated fatty acids C18:2 was the main factor determining the oil quality of safflower seeds.

To gain a better understanding of the relationship between genes and fatty acids species, the Pearson correlation test was performed for the intensity of fatty acids and the expression pattern of genes during the safflower seeds development stage. Our results showed that a total of 28 genes were significantly correlated with C18:1, C18:2 and C18:3 molecular species metabolites that exhibit a Pearson correlation coefficient > 0.7 and p-value < 0.05. Among them, expression pattern of 15 FAD2 genes (Cti _chr11_01896, Cti_chr9_01626, Cti_chr11_01899, Cti_chr11_01897, Cti_ chr9_01627, Cti_chr11_01898, Cti_chr9_01634, Cti_chr9_01616, Cti_chr9_01625, Cti_chr9_01617, Cti_chr3_02112, Cti_chr3_02111, Cti_chr11_01894, Cti_chr10_00208, Cti_chr4_00382) and 4 FAD6 genes (Cti_chr11_01893, Cti_chr7_00474, Cti_chr11_01895, Cti_chr3_02287) were positively correlated with C18:1n7, C18:1n9 and C18:2n6 composition patterns during seed developing stages (Fig.  6 ). Importantly, two FAD6 genes Cti_chr11_01893 and Cti_chr11_01895 expression patterns showed significant correlation with C18:2 contents during seed development stage. These results indicated that FAD2 and FAD6 genes appear to be responsible for the high proportion of C18:2 in developing safflower seeds.

Fatty acids biosynthesis and contents of seed lipids. ( a ) Fatty acid and oil biosynthesis in safflower. KAS II, β-ketoacyl-ACP synthetase; SAD, stromal stearoyl-ACP desaturase; FATA, acyl-ACP thioesterase; G3P, glycerol-3-phosphate; GPAT, glycerol-3-phosphate acyltransferase; LPA, lysophosphatidic acid; LPAAT, Lysophosphatidic acid acyltransferase; PA, phosphatidic acid; FAD2/3/6/7, Fatty acid desaturase; DAG, diglycerides; TAG, triglycerides; ( b ) Fatty acids contents of seed storage lipids in different developing stages

Correlation coefficient between gene expression level and contents of fatty acids. * p  < 0.05

In the present study, we report the complete genome sequence of an economically important crop safflower. We presented valuable insights into the genetic organization of safflower, which facilitates the identification of key functional genes implicated in fatty acid synthesis. These valuable genomic resources could be easily accessible to researchers in the field for future functional and molecular breeding studies. Previous studies on the Compositae have reported genome sequences for H. annuus [ 31 ], lettuce ( Lactuca sativa ) [ 32 ], and globe artichoke ( Cynara cardunculus var. scolymus) [ 30 ]. Those studies have provided scientific resources for comprehensive analyses of genome evolution, functional gene exploration, metabolic pathway construction, and molecular breeding programs.

In light of our results, we revealed a high-quality safflower genome, with a size of 1,061.1 Mb and 12 pseudochromosomes. There are many karyotypes in the ancestor species of safflower with 10, 11, 12, 22, and 32 pairs of chromosomes, many of which are self-incompatibility species [ 40 ]. The current karyotype of cultivated safflower could have originated from wild ancestor C. tinctorius , with 2n = 24 chromosomes karyotype. This high-quality genome information will be useful for analysing sequences of homologous species, and provides genetic evidence for the nutritional compounds encoded in the safflower genome. In addition, our analysis also revealed that 63.4% of the assembled genome comprises repetitive sequences. This percentage is notably close to that of artichoke (58.4%), yet lower than observed in sunflower (74.7%) and lettuce (74.2%). The relatively larger genome size of sunflower and lettuce could be related to the larger amount of repetitive sequences. It is widely believed that transposable elements play a dominant role in the growth of genome size, and much of the variation in plant genome size can be attributed to the continuous accumulation of these transposable elements. For instance, the sunflower genome is 3.6 Gb and the lettuce genome are 2.38 Gb, which are nearly two to three times of artichoke genome (1.08 Gb) and safflower genome (1.06 Gb). Although, for sunflower genome, the influence of WGD event should be take into consideration regarding the large genome size, our analysis also suggests that repetitive sequences have contributed significantly to the genome size of both sunflower and lettuce. The disparities in repetitive sequence content provide crucial insights into the genomic architecture of these plant species. The higher proportion of repetitive elements in sunflower and lettuce genomes may contribute to their larger genome sizes compared to artichoke and safflower.

First safflower ( Carthamus tinctorius L.) cultivar ‘Anhui-1’ genome was sequencing using PacBio Sequel (Pacific Biosciences) combined with Illumina Hiseq 2500 sequencing platform and focused on biosynthetic pathways of LA and HSYA [ 25 ]. Here, in this work, we sequenced and denovo assembled genome of safflower cultivar ‘Jihong01’ using BGI-SEQ500 and Oxford Nanopore Technologies (ONT) platform and gained another high-quality genome assembly results. Meanwhile, we paid more attention to UFA contents than saturated fatty acid during seed development stages. Seed oil fatty acids composition continues to be important trait for safflower breeding [ 41 ]. Recent studies on the molecular mechanisms of lipid metabolism have identified a number of genes that form the genetic basis of this trait. The factors determining seed oil composition were found to be complex. In cultivated safflower, lipid metabolic pathways underlie the natural trait of seed oil content, and candidate genes in the genome were identified to be involved in lipid metabolism and reported before. The unsaturated fatty acid synthesis in ER is important during safflower seed development. Our analyses indicated that the genes involved in fatty acids composition in safflower seeds have undergone expansion during evolution. These analyses may provide essential clues about the biochemical relevance of lipid composition in seeds.

In terms of the fatty acid composition of oil, there is a lower proportion of LA in sesame (C18:2, 32.95–52.94%) [ 42 ] than in safflower (C18:2, 63.9–76.1%) [ 41 , 43 , 44 ]. However, the number of genes involved in fatty acid elongation, biosynthesis, and degradation are similar among the genomes of safflower, sunflower, sesame [ 42 ], grape [ 45 ], capsicum [ 46 ], and Arabidopsis [ 47 ]. A few key enzymes in the desaturation metabolic pathway regulate unsaturated fatty acid biosynthesis in the ER. Genetic evolution, including genome duplication or gene family expansion, is crucial for generating new gene functions and/or for intensifying pathways [ 48 , 49 ]. Divergence from an ancestral genome can result in an evolutionary bias towards the production of specific natural products. The emergence of duplicates can result in gene expansion, contraction, or loss [ 50 ]. FAD2 gene family encoding enzymes that catalyse linoleic acid biosynthesis has expanded via tandem duplication and formed two gene clusters located on chromosome 9 and chromosome 11 respectively. The result indicated that tandem duplication possibly contributed to the expansion of the gene families in safflower. In particular, the FAD2 and FAD6 homologs involved in unsaturated fatty acid biosynthesis showed the highest transcript levels at the DAF18 and DAF24 stage of seed development. Previous studies found that their expression patterns were related to the LA content, with high transcript levels during seed development [ 41 , 51 ]. These findings provide substantial novel insights into the reasons for the high proportion of LA in safflower oil.

The assembled genome sequence of safflower mostly consisted of repeats, coding and non-coding RNAs, and other related sequences. This information allowed us to reconstruct the evolutionary history of safflower, which includes a large-scale safflower-specific whole-genome duplication events. Candidate genes, including FAD2 and FAD6 , which encode key functional enzymes related to LA composition. FAD2 families were expanded in safflower, and correlation analysis of gene expression alongside contents of fatty acids indicated that the specific FAD2 and FAD6 genes could be responsible for the synthesis of a wide range of LA.

Conclusions

The safflower genome assembly represents a cornerstone for future research programs aimed at exploiting the economic properties of safflower, while also considering agricultural constraints and human nutritional needs and for advancing molecular breeding programs aimed at producing new safflower cultivars. The candidate FAD2 and FAD6 genes revealed by our integrated approach provide a genetic resources of unsaturated fatty acid biosynthesis and provide a genetic landscape for safflower germplasm utilization.

Experimental procedures

Dna extracting and sequencing.

The plant material of safflower ( Jihong01 cultivar, deposited in Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, JLAU) used in this study was identified by Yuanyuan Dong. Safflower variety seedlings ( Jihong01 ) collected and planted in an experimental field of Jilin Agriculture University, Changchun City, China were used in this research and stored in Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education. High-quality genomic DNA from Jihong01 leaves was extracted using the MolPure® Plant DNA Kit (Yeasen, China). Subsequently, the extraction process focused on selecting large-size fragments, which were accomplished through automated Blue Pippin system. Following this, the DNA underwent treatment involving the end-repair/dA tailing module, and subsequently, it was ligated to an adaptor using the ONT 1D ligation sequencing kit. The prepared library was loaded onto flow cells and subjected to sequencing using the Nanopore PromethION platform.

Genome assembly

K-mer frequency was calculated by Jellyfish v2.26 [ 52 ] and the genome size was estimated using GenomeScope [ 53 ]. The initial contigs were assembled by NECAT with default parameters using Nanopore reads longer than 5 kb. The initial assembly was error-corrected by Pilon with short reads. Size of the initial assembly was a little larger than estimated, so we used HaploMerger2 software [ 27 ] to remove redundant contigs in the initial assembly. Then, the assembly was error-corrected again. Reads generated by Hi-C library were filtered strictly by HiC-Pro pipeline [ 54 ] to remove invalid reads pairs. We used Juicer [ 55 ] and 3D de novo assembly (3D-DNA) pipeline [ 56 ] to anchor contigs to pseudochromosomes.

Repeat annotation and LTR insertion time

Repetitive sequences were annotated using a combination of de novo and homology strategy. We used RepeatModeler [ 57 ], LTR_FINDER [ 58 ] and TRF [ 59 ] software for de novo repeats identification based on repetitive sequences features. Then RepeatMasker and RepeatProteinMask were used to annotate transposon elements based on RepBase. LTR insertion time was estimated based on the divergence of LTR pairs. Intact LTRs were identified using LTR_FINDER software in the four Compositae genomes. Then we used MUSCLE [ 60 ] to align LTR pairs and distmat to calculate K values under the Kimura two-parameter model. With the K values of LTR pairs, the insertion time was calculated using formula T = K/2r , where r was the rate of nucleotide substitution and set as 7 × 10 − 9 per site per generation here [ 61 , 62 ].

Genes prediction and function annotation

Protein-coding genes were predicted based on both homolog proteins and transcripts. Proteins of seven plants species ( Arachis hypogaea (GCF_003086295.2), Brassica napus (GCF_000686985.2), Glycine max (GCF_000004515.5), Helianthus annuus (GCF_002127325.1), Lactuca sativa (GCF_002870075.1), Ricinus communis (GCF_000151685.1) and Sesamum indicum (GCF_000512975.1)) was downloaded from NCBI database. We first aligned these proteins with the assembly using BLAT [ 63 ], then the alignment was input to Genewise [ 64 ] to get homology annotations. RNA-seq reads were mapped to the assembly using HISAT2 [ 65 ] and transcripts were assembled using StringTie [ 66 ]. All of the evidences were integrated to the final protein-coding gene set by GLEAN [ 67 ]. Protein-coding genes were assessed for conserved protein domains in the ProDom, ProSiteProfiles, SMART, PANTHER, Pfam, PIRSF and ProSitePatterns databases using InterProScan [ 68 ]. Also, amino acid sequences were aligned to the following protein databases: Swiss-Prot, TrEMBL, Kyoto Encyclopaedia of Genes and Genomes (KEGG) using BLASTP (e-value < 1e-5) for function annotation.

Comparative analysis

All protein-coding gene sequences of the 10 oil plant species ( Elaeis guineensis (GCF_000442705.1), Glycine max , Helianthus annuus , Jatropha curcas (GCF_000696525.1), Juglans regia (GCF_001411555.1), Linum usitatissimum (Linum usitatissimum v1.0), Olea europaea (GCF_002742605.1), Ricinus communis , Sesamum indicum and Zea mays (GCF_000005005.2)) were downloaded from the NCBI or Phytozome database. The longest transcript of each gene without frame shift or internal termination was selected and translated into amino acid sequences for subsequent analyses. First, we used BLASTP for an all-to-all proteins alignment under the e-value of 1e-5. Then the ortholog genes were clustered into groups using OrthoMCL with a Markov inflation index of 1.5 and a maximum e-value of 1e-5. One-to-one single-copy ortholog groups were joined to a super-gene (single-copy orthologous genes are composed of head-to-tail connections) and aligned using MUSCLE [ 60 ]. Phylogenetic tree was constructed using RAxML [ 69 ] with Z. mays and E. guineensis as outgroups, under GTR + Optimization of substitution rates and GAMMA model of rate heterogeneity. The divergence time was estimated using MCMCTREE in PAML packages [ 70 ] based on HKY85 model and correlated rates molecular clock model. The size changes of each gene families were calculated by CAFE [ 36 ] with the random birth and death model.

WGD events and synteny

We used WGD software [ 37 ] to identify WGD events in the evolutionary process of safflower, sunflower, lettuce, artichoke (GCF_002870075.1) and coffee tree (AUK_PRJEB4211_v1). Synteny blocks between safflower and sunflower and between safflower and coffee tree were identified and displayed using jcvi packages [ 71 ].

Identification of unsaturated fatty acids biosynthesis genes

We used BLASTP to identify safflower FAD2 and FAD6 based on amino acids sequences of Arabidopsis thaliana FAD2 (NP_187819.1), FAD6 (NP_194824.1) with e-value of 1e-10.

Fatty acids content analysis

Safflower seeds ( Jihong01) were sourced from Engineering Research Center of Bioreactor and Pharmaceutical Development, Ministry of Education, JLAU. Dry seed samples (DAF6 (6 days after flowering), DAF12, DAF18, DAF24, DAF30) were collected at five different stages of seed development for the purpose of analysing fatty acid content and composition. Methyl esters (FAME) were prepared from each seed sample. Subsequently, quantitative analysis of fatty acids within these FAME samples was conducted utilizing Gas Chromatography-Mass Spectrometry (GC-MS) through the Agilent Technologies 6890 N/5975B system. The methods employed for this analysis were in accordance with those described by Ecker et al. [ 72 ]. The fatty acids present, including saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs), were subjected to quantitative calculations. These calculations were carried out based on a standard fatty acid methyl ester mix.

RNA sequencing

Total RNA was extracted from the 5 different developing seeds (DAF6 (6 days after flowering), DAF12, DAF18, DAF24, DAF30) using a TRIzol Plus RNA Purification Kit following the manufacturer’s instructions. RNA integrity and quantity were confirmed using an Agilent 2100 Bioanalyzer. The mRNA was hybridized with an Oligo(dT) probe and captured using magnetic beads. Subsequently, the mRNA was fragmented at high temperature and reverse-transcribed into first-strand DNA. This first-strand DNA served as a template for the synthesis of second-strand DNA, resulting in the formation of double-stranded DNA (dsDNA). Adaptors with dTTP tails were ligated to both ends of the dsDNA fragments. The ligation products were then amplified via PCR and circularized to generate a single-stranded circular (ssCir) library. The ssCir library was further amplified through rolling circle amplification (RCA) to produce DNA nanoballs (DNB). Finally, the DNBs were loaded onto a flow cell and sequenced using the DNBSEQ platform. Each sample was sequenced three times in triplicate.

Data availability

The raw sequence reads were deposited in China National GeneBank DataBase (CNGB db) under Project No. CNP0004859 and CNP0004861.

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Acknowledgements

This work was supported by China National GeneBank (CNGB).

This research was funded by The Science and Technology Development Project of Jilin province (20210402044GH, 20220101354JC), Science and Technology Research Project of the Education Department of Jilin Province (JJKH20220325KJ).

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Yuanyuan Dong and Xiaojie Wang Contribute equally to this work.

Authors and Affiliations

Engineering Research Center of Bioreactor and Pharmaceutical Development, College of Life Sciences, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China

Yuanyuan Dong, Naveed Ahmad, Yepeng Sun, Yuanxin Wang, Xiuming Liu, Na Yao, Yang Jing, Linna Du, Xiaowei Li, Nan Wang, Weican Liu & Fawei Wang

School of Pharmaceutical Science, Key Laboratory of Biotechnology and Pharmaceutical Engineering of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, China

Xiaojie Wang & Xiaokun Li

Sanya Nanfan Research Institute of Hainan University, Sanya, 572025, China

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Y.D., X.W., X.L., and H.L. performed some data analyses. J.Y., N.Y. and L.D. managed samples and tissues. Y.W. prepared materials and uploaded data. Y.D., X.W., X.L., and J.Y. performed some data analyses and prepared graphics. N.Y., X.L., N.W., X.L., and W.L., prepared the libraries. H.L., and X.L. assisted in data analysis and in the overall design of the project. F.W., H.L., and X.L. developed the figure of the study and assisted with manuscript preparation. Y.D., X.W., N.A. Y.S. X.L., J.Y., F.W., and H.L. wrote and revised the manuscript. All of the authors reviewed and approved the final manuscript.

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Correspondence to Haiyan Li .

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No specific approval was required for voucher specimens for this study. Voucher specimens were prepared and deposited at the Jilin agricultural University. Yuanyuan Dong and Xiaojie Wang undertook the identification work of the plant material. The authors have complied with all relevant institutional and national guidelines and legislation in experimental research and field studies on plants, including the collection of plant materials for this study.

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Dong, Y., Wang, X., Ahmad, N. et al. The Carthamus tinctorius L. genome sequence provides insights into synthesis of unsaturated fatty acids. BMC Genomics 25 , 510 (2024). https://doi.org/10.1186/s12864-024-10405-z

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Received : 19 September 2023

Accepted : 10 May 2024

Published : 23 May 2024

DOI : https://doi.org/10.1186/s12864-024-10405-z

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