Mastering the ASHG Abstract Review Process: Select the Right Topic

Posted By: Kiran Musunuru, 2019 Chair, ASHG Program Committee

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Kiran Musunuru, 2019 Chair, ASHG Program Committee

As you are preparing your ASHG 2019 abstract, I wanted to take some time to share how the ASHG topics and subtopics are structured and guidance on how to select the right topic. Understanding this will help you score better during review and get your talk or poster in front of the right people.

How ASHG Topics are Structured

Each of the twelve topics covers a large portion of current research in human genetics and are organized to group the most similar abstracts together. The topics and subtopics form the basis of the abstract review and session building process and, eventually, the organization of the poster hall. Program Committee members are assigned to review an abstract topic aligned with their research expertise.

With an average of 3,500 abstracts submitted, it has been helpful to further divide the topics into subtopics based on organ systems and clinical phenotypes. The subtopics are the same regardless of the main topic chosen. When Program Committee members gather to draft the Platform Sessions in July, they will often use the subtopics to build cross-topic sessions covering the most exciting research.

Changes to the Topics to Keep Up with the Field

The topic/subtopic system was last reorganized in 2016. Given the pace of expansion in human genetic research, the Program Committee reviewed and revised the topics this year. The largest changes were the addition of two topics. “Precision Medicine, Pharmacogenomics, and Genetic Therapies” was added to address the rise in genetic therapy development in recent years. “Molecular Effects of Genetic Variation” expands upon the previous “Genome Structure and Function” topic, so that we may group together all the functional genetics and gene expression abstracts that were previously spread across several abstract topics. Look for the new topics as you browse posters in Houston.

Tips for Selecting the Right Topic

Selecting the correct topic for your research is important to make sure it is reviewed by the appropriate experts and programmed with similar abstracts in either an oral or poster session. Each topic is represented proportionally in the talks, so there is no advantage to selecting one topic over another. In fact, submitting to the wrong topic will likely result in a poorer score because experts from other fields may view your work as less compelling.

Before submitting your abstract, make sure you read the definitions for each of the twelve topics. Determine which topic is most likely to have closely related studies to yours, as that is likely the best fit. Taking a few extra minutes to find the right home for your abstract will help you achieve the best possible score and boost your visibility with relevant colleagues.

Submit by June 6, 2019, to have your work considered for ASHG 2019. Then, check out the overview of ASHG’s abstract review process and register to see all your colleagues’ impressive research.

Kiran Musunuru, MD, PhD, MPH, 2019 Program Committee Chair, is an Associate Professor of Cardiovascular Medicine and Genetics, and the Director of the Cardiovascular Institute’s Genetic and Epigenetic Origins of Disease Program, at the Perelman School of Medicine at the University of Pennsylvania.

Communication and Documentation Standards at Biocuration 2019

Posted By: Marina DiStefano, PhD, ASHG Communications Committee

I recently returned from the ISB Biocuration 2019 conference in Cambridge, UK. To me, this year’s conference focused on two of the core goals of the International Society for Biocuration (ISB): one, to promote communication and exchanges between curators and two, to encourage best practices by providing documentation on standards and annotation procedures.

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The group at the 2019 ISB Conference (photo courtesy of: George Georghiou)

Communication and Exchanges between Curators

Many presenters encouraged sharing of database resources and curation materials so as not to duplicate efforts and to facilitate transparency. For example, Rolf Apweiler, director of EMBL-EBI, discussed the Alliance of Genome resources, an effort to locate all curations of model organisms on the same website in a standardized format. The Alliance is founded by FlyBase, Mouse Genome Database, the Gene Ontology Consortium, Saccharomyces Genome Database, Rat Genome Database, WormBase, and the Zebrafish Information Network and contains information about six model organisms. In a related vein, Niklas Blomberg, director of ELIXIR, pointed out that many of the curation resources used by the entire scientific community are reliant on grant funding, making their future existence unstable. He discussed how resources should be defined as Core Data Resources to potentially solicit permanent stable funding.

There were also interactive workshops each afternoon that further supported this idea of communication between curators. One workshop, in which I presented, discussed the efforts of the Gene Curation Coalition (GenCC). This Coalition is an international group of gene curation resources with the goal of harmonizing the terms for defining clinical validity of gene:disease relationships. Three GenCC member groups (ClinGen, Genomics England PanelApp, and Orphanet) each took turns presenting their gene curation strategies. Participants were able to discuss the similarities and differences between the approaches. The workshop ended with survey results from the scientific community about the gene:disease validity terms.

Documentation and Standards

The more time I spend as a curator, the more I understand the value of consistent curation language. This idea was heartily supported by presenters at the conference who encouraged use of ontologies and the idea that each curation resource should strive to abide by FAIR (Findable, Accessible, Interoperable, and Reusable) data standards. Varsha Khodiyar, data curation editor at the journal Scientific Data, discussed how Springer Nature is trying to support FAIR data sharing to help reduce irreproducible experiments. Sirarat Sarntivijai, ELIXIR interoperability platform coordinator, spoke about recommended interoperability resources, tools that could be used by curators, creators of websites, or even authors to make data FAIR.

Many talks about specific resources, such as SIGNOR/DISNOR, SwissLipids, and the BioGRID Interaction database, cemented the idea that resources are most useful when they use ontologies to categorize terms.

The four days of this conference were a fascinating and important glimpse into the world of curation resources. After attending, it is quite clear that many of these resources are critical to the scientific community and keep research moving forward, thanks to the hard work of all the biocurators. The poster sessions were intimate and allowed for thoughtful discussion, useful suggestions, and hopefully the start of budding collaborations. Workshops were very interactive, and it was clear that the curators harbor a passion for their field of work and the work of their fellow curators.

If you have ever done or are planning on doing any curation, I highly recommend you attend this conference. The 13th International Biocuration Conference takes place in Bar Harbor, Maine from May 17-20, 2020.

Marina DiStefano, PhD, is a member of the ASHG Communications Committee and a postdoc at Harvard Medical School. She has been a member of ASHG since 2018.

Be Well to Do Well

Posted By: Ann Klinck, Communications and Marketing Assistant, ASHG

Earlier this month, ASHG hosted a webinar titled Resilience and Wellness, which focused on strategies to maintain your mental wellness in the scientific workplace and improve your resilience to the challenges and setbacks we all face.

Sharon Milgram, PhD, Director of the Office of Intramural Training and Education (OITE) at the National Institutes of Health (NIH) reminded webinar listeners that to function at the highest capability, you must take your own well-being into consideration.

Developing Resilience

“Those who are resilient prepare to be resilient,” said Dr. Milgram. Developed through education, self-reflection, and practice, resilience can help a person navigate through adversity constructively. Here’s how:

  • People: Find people you can trust, who will give you energy when you feel stuck, and go to them to find compassion, a listening ear, or just companionship.
  • Process: Figure out what wellness practice or resources you can focus on that will help you in that moment.
  • Prepare: You cannot try to discover these things in a moment of crisis; you have to set yourself up for success.

Dr. Milgram also provided this helpful tool to identify characteristics of a resilient person.

Handling Our Inner Critic

To improve the way you view difficult situations or setbacks, analyze your self-talk. Are the stories you tell yourself harsher than they need to be? Consider whether you would say the things you tell yourself to a friend. Are you seeing the broader picture?

Destroying Cognitive Distortions

Dr. Milgram described cognitive distortions or automatic negative thoughts as “Characteristic ways that our mind convinces us of something that is really not true to reinforce negative thinking or emotions.” Some examples are:

  • All-or-nothing thinking: Your performance is either perfect or a complete failure.
  • Catastrophizing: You exaggerate the implications of a setback or mistake.
  • Mind reading: You make assumptions about what someone else is thinking.

Here’s how to tame them:

  • Journal to identify your most common negative thoughts.
  • Talk to mentors and peers.
  • Use your science voice to question them: Where is the evidence that this is the worst thing to ever happen in my life?
  • Be open to counseling when it’s unmanageable.

Never Feel Like an Imposter

Imposter fear is a type of cognitive distortion, qualified as “The feeling of phoniness in people who believe that they are not intelligent, capable, or creative despite evidence of high achievement.” Dr. Milgram pointed out that “If you are working towards a PhD in the sciences, if you are a postdoc, if you have been working as an undergraduate in a high-knowledge research environment, there is much evidence of high achievement already, though we often find ourselves feeling like fakes and phonies.”

Imposter fears include attributing success to luck or discounting your successes. You’re not alone! 70+% of individuals experience imposter fears at some point in their educational and work journey. Fight that feeling by practicing accepting praise and reminding yourself that impostor fears happen to everyone.

To Do Well, We Have to Be Well

Dr. Milgram provided a model of holistic self-care outlining four quadrants of wellness.

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In her shared slide deck, you can find a wellness assessment for each quadrant. While everyone defines these quadrants differently, each needs to be fulfilled to feel well. Dr. Milgram reminded us we can’t fix everything at once, and to take time to work on one area instead of trying to change too many habits too quickly.

Watch the full webinar, or check out our Twitter account to see live engagement from listeners!

Inside AJHG: A Chat with Susan Slaugenhaupt

Posted By: Sarah Ratzel, PhD, Science Editor, AJHG 

Each month, the editors of The American Journal of Human Genetics interview an author(s) of a recently published paper. This month, we check in with Sue Slaugenhaupt to discuss her paper, “ELP1 Splicing Correction Reverses Proprioceptive Sensory Loss in Familial Dysautonomia”.

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Slaugenhaupt Lab (photo courtesy of Dr. Slaugenhaupt)

AJHG: What caused you to start working on this project? 

Sue: When I arrived at Massachusetts General Hospital as a postdoctoral fellow in 1991, one of the projects in Jim Gusella’s lab was focused on mapping the gene for familial dysautonomia (FD). Given my background in gene mapping, I became involved in the project and once we mapped the gene, I took over the project aimed at identifying the mutation. Once we cloned the gene and discovered that it was a mRNA splicing defect, I became fascinated by the idea of modifying splicing as a route to therapy, and my lab has worked on this ever since. I have known many FD patients and their families for over 25 years, and our work is driven by the desire to develop a disease modifying therapy for this devastating disease.

AJHG: What about this paper most excites you? 

Sue: Developing a mouse model for FD was a huge challenge since the disease is caused by a tissue-specific reduction of ELP1 protein. In 2016, we succeeded in generating a phenotypic mouse model and this paper describes the first trial of a potential therapy in our mouse. I am very excited that our treatment was able to increase the amount of ELP1 protein in the peripheral nervous system and, most importantly, rescue two of the most debilitating aspects of the disease, gait ataxia and kyphosis.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Sue: There are many efforts underway to generate therapies that target mRNA splicing, including small molecules, antisense oligonucleotides, and exon-specific U1 snRNAs. A significant fraction of human genetic disease mutations impact mRNA splicing, so this is an exciting time. These therapies are targeted at the molecular mechanism of disease, not at symptoms, and we are likely to see new treatments for many previously untreatable genetic diseases over the next several years.

AJHG: What advice do you have for trainees/young scientists?

Sue: Find a good mentor. One who cares more about your future and your career than their own. Look outside your own lab, and fight against the tide that keeps you locked in an unproductive situation too long.

AJHG: And for fun, tell us something about your life outside of the lab.

Sue: I’m moving to a condo overlooking the beach next month and I can’t wait!

Susan Slaugenhaupt, PhD, is Scientific Director, Center for Genomic Medicine at Mass General Hospital Research Institute and Professor of Neurology at Harvard Medical School. She is a member of ASHG’s Board of Directors.

 

Why is a 2011 Budget Relevant to Science Funding Today?

Guest Post By: Mary Woolley, President and CEO, Research!America

Each year, Congress develops a federal budget, which establishes funding for each federal department and agency for the following fiscal year. This determines how much funding agencies like the NIH have to support scientific research through grants, as well as in their own labs.

Budget Caps Threaten Research Funding

A federal law, the 2011 Budget Control Act (BCA), placed stifling caps on spending that have threatened funding for the NIH and other agencies. These caps are blunt tools that batter crucial national priorities, compromising security, prosperity, and progress.

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Research!America and partner organizations, including ASHG, are running ads urging Congress to #RaisetheCaps. (courtesy Research!America)

Why It’s Time to #RaisetheCaps

Because the caps established by the BCA are so low, Congress has raised them repeatedly to allow sufficient funding for federal agencies. Unfortunately, those “caps deals” were temporary. Unless Congress acts again, we’re looking at a cut of approximately $55 billion to non-defense discretionary spending in the next fiscal year, which guarantees trouble. If the cuts are distributed evenly or no budget deal is reached, then NIH and every other public health and science agency faces a cut of about 10%. In the case of NIH, that would mean a cut of as much as $4 billion.

Achieving another agreement to raise the budget caps is crucial, time-sensitive, and not by any means a sure thing.

You don’t need a laundry list of the negative consequences on science that these cuts would engender. Suffice it to say that promising research will be choked off, fewer new grants will be funded, and medical and other scientific progress will slow dramatically. All this during a time of unprecedented scientific opportunity, when other nations are already nipping at our heels and would surely attract more and more young scientists if the U.S. signaled lack of support. Starving research is not the solution to what ails us — literally or economically.

Your voices, your story, and your expertise are needed now. Tell your friends, colleagues, and Congressional representatives why medical progress, public health progress, and science itself are crucial, and why federal funding for these priorities is so important.

Research!America, supported by partner organizations including ASHG, has created resources for you to advocate for federal research funding. Additional resources and tools to urge your representatives to #RaisetheCaps are available on ASHG’s Advocacy Center.

 

Defining the Responsibility to Recontact Research Participants

Posted By: Staff

This week, ASHG and eight partner organizations issued a position statement outlining whether, and to what extent, there is a responsibility to recontact genetics and genomics research participants when new findings emerge that suggest their genetic information should be interpreted differently.

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Today, ASHG and partner organizations issues a statement in AJHG addressing the responsibility to recontact research participants.

Variants of uncertain significance get reclassified at a relatively high rate – up to half of such variants have been reclassified in the past decade. One paper found that 12% of these reclassifications had the potential to alter clinical management.

We sat down with Yvonne Bombard, PhD; and Howard Levy, MD, PhD, lead authors on the statement, to get their take on the issue.

ASHG: Why did the Social Issues Committee tackle this topic?

Yvonne: Genetics and genomics researchers are at the forefront in collecting and analyzing data related to sequence variant interpretations, which is continuously evolving. This means that a variant’s clinical significance might be reinterpreted over time as new evidence emerges regarding its pathogenicity or lack thereof. This raises ethical, legal, and financial issues as to whether there is a responsibility to recontact research participants to provide updates on reinterpretations of variants after the initial analysis.

While clinical recommendations on the responsibility to recontact research participants with such reinterpretations have begun to emerge, the Social Issues Committee decided to tackle this topic because there is a lack of guidance on the responsibility for researchers. We were fortunate to have collaborative partners on our Workgroup from clinical, research, and laboratory settings across various countries and jurisdictions. The statement reflects their synergistic efforts and the care these members took to carefully craft a comprehensive set of recommendations.

Howard: Perhaps the most obvious but most important concept in this position statement is the recognition that recontacting individuals to keep them abreast of new knowledge is a desirable and laudable goal. The problem is that we live in a world of limited resources, and the cost of achieving this goal can be onerous.

As Yvonne points out, there is only limited guidance on recontact in the clinical arena, and none in the research arena. ASHG and our partner organizations are fortunate to count among our memberships expert clinicians, researchers, laboratorians, educators, counselors, social scientists, bioethicists, lawyers, and patient advocates from around the world. We are uniquely suited to address this topic with the broadest possible representation and perspective.

There is a long history of thinking about clinical care and research as independent, non-overlapping contexts. But in recent years we’ve been recognizing and grappling with the reality that the lines between the two are blurry and sometimes not well-defined. In genetics, many of us serve in both roles concurrently, which can create real or perceived conflicts of interest. It is incumbent on all of us to work as hard as we can to be aware of these potential conflicts and respond appropriately. Having principled and evidence-based guidelines upon which to rely is an invaluable resource in helping us to evaluate these situations and determine the right course of action.

ASHG: What are the key differences between the research and clinical contexts?

Howard: While the intent of biomedical research is ultimately to improve or maintain health and avoid, treat, or cure disease, the proximal goal is to generate knowledge that forms the foundation of that ultimate benefit to society. Direct benefit to individual research participants is wonderful when it occurs, but is not the primary purpose of the research. Conversely, clinical care puts the benefit of the patient front and center as the primary goal.

Thus, in the clinical context, recontact can be argued as furthering the goal of maintaining information and informed consent, so that individual benefits can be maximized and individual harms minimized. But in the research context, the ethical desirability of recontact is not as strong, because the main goal is generation of new knowledge, not individual benefit. In fact, recontact in the research context can be argued as ethically undesirable if the recontact consumes so much resource that the research itself can’t be completed. In addition, while there are mechanisms available to seek at least partial financial compensation for clinical recontact on a case-by-case basis, there is no such funding mechanism in the research context.

Yvonne: The workgroup carefully considered differences between the research and clinical contexts to determine a reasonable set of floor/ceiling recommendations, balancing these imperatives across research and laboratory settings. We also developed a decision tree, which walks a researcher through whether and how to implement these recommendations within their particular research context.

ASHG: What factors affect the strength of the responsibility to recontact?

Yvonne: The workgroup considered a variety of factors that would affect the strength of the responsibility to recontact, and recommended that this responsibility is stronger when:

  • The research is active, ongoing, has funding, and participant contact details are up-to-date
  • The informed consent process set an expectation of potential contact or recontact
  • There is high certainty about the new interpretation of the genetic variant
  • The reinterpretation would be relevant to the condition being investigated

If the interpretation of a given variant is related to the condition under study or reasonably expected to affect participants’ medical management, the Workgroup recommended that there is a strong responsibility for researchers to attempt to recontact participants to offer updated results. If the reinterpretation is not expected to affect medical management, recontact is advised rather than strongly recommended.

Conversely, the statement recommends that there is no responsibility for researchers to hunt or scan the genomic literature for changes in variant interpretation, and that any responsibility to recontact should be limited to the duration of research funding. Additional recommendations address the practicalities of informed consent, involvement of institutional review boards, timeliness and protocol of recontact, and structuring of future research studies.

Howard: Clinical utility to the participant is prioritized higher than personal utility or benefit to family members. And issues of practicality have to be considered, too. Some of these judgments may be subject to bias, and we therefore encourage consultation with and input from IRBs, ethics boards, and clinical consultants.

ASHG: How might advances in IT address practical challenges in fulfilling this responsibility?

Yvonne: Advances in IT will likely reduce the opportunity costs of recontact and open up new avenues of keeping patients and research participants informed. Most electronic medical record systems and many clinical laboratories now offer portals through which patients might see their data, interact with clinical, laboratory, and support staff, and access educational material. As our IT resources and our databases continue to evolve, it is plausible that much of the effort of recontact could become automated. When a variant is reclassified, an automated notification could be sent to all patients and research participants known to harbor that variant, alerting them of the revised interpretation and prompting them to log into the portal to view the new information and associated material.

Howard:  As the volume of identified and re-interpreted variants continues to increase, IT solutions will be critical to handling these immensely large numbers at scale, at much lower cost, and more rapidly than doing so manually.

IT solutions can also reduce the risk of biased or uneven approaches to attempting recontact. Humans may consciously or subconsciously vary their method of communicating information, and sometimes make mistakes in adhering to informed consent, research protocols, and other policies governing the recontact process. An automated, algorithmic approach is still subject to human bias and error in creating and implementing the rules that drive the process, and is obviously not as personal as direct human communication, but is by definition consistent from case to case.

ASHG: What infrastructure would be needed to maximize the impact of such IT advances?

Yvonne: This future vision depends upon well-developed and interoperable databases, including both the interpretations of the variants and the lists of who has each variant. Potentially difficult questions about identity and privacy will need to be answered. There are also significant concerns about the “digital divide” and economic disparities; increasing reliance on IT solutions has the potential to create disparities among people who are unable to or choose not to utilize such resources. There will always be situations that require more nuance and explanation than an automated algorithm can achieve. But there is hope that IT enhancements can significantly lower the costs and barriers to recontacting research participants when it is considered desirable to do so.

Howard: Perhaps more challenging than creating the infrastructure of standardized and interoperable databases will be establishing societal and cultural expectations surrounding privacy, security and sharing of the data, and developing the necessary IT tools to collect, maintain, revise, and respect individuals’ preferences regarding such data sharing. With all of that in place, patient-facing portals built into IT systems and yet-to-be-developed apps can deliver timely and relevant information to consumers who choose to receive it, and pair that information with additional education and support modules to help them make the most of that information.

Yvonne Bombard, PhD, is an Assistant Professor at the University of Toronto Institute of Health Policy, Management and Evaluation; Director of the St. Michael’s Hospital Genomics Health Services Research Program; and Scientist at the St. Michael’s Li Ka Shing Knowledge Institute. Howard P. Levy, MD, PhD, is an Associate Professor in the Division of General Internal Medicine & McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University. 

Inside AJHG: A Chat with Nancy Cox

Posted By: Sara Cullinan, PhD, Deputy Editor, AJHG

Each month, the editors of The American Journal of Human Genetics interview an author of a recently published paper. This month we check in with Nancy Cox to discuss her paper “GRIK5 Genetically Regulated Expression Associated with Eye and Vascular Phenomes: Discovery through Iteration among Biobanks, Electronic Health Records, and Zebrafish.”

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Nancy Cox, PhD (photo courtesy Dr. Cox)

AJHG: What prompted you to start working on this project? 

Nancy: I presented some of the preliminary studies from this work at a work-in-progress meeting at Vanderbilt, and Ela Knapik, who directs the zebrafish core here, saw the presentation and asked the question at the end, “Why don’t you knock out GRIK5 in zebrafish?” And so we talked afterward and agreed to collaborate on this project. I expected it to take forever — I was totally unprepared for how rapid CRISPR can be. But it has been a fantastic collaboration and we are working together on several additional really fun projects now.

AJHG: What about this paper/project most excites you? 

Nancy: Trying to understand how polygenic contributions to disease work is challenging because the effect sizes for any individual variant are quite small. This was a different kind of discovery because we had used a gene-based method and found associations to a pattern of phenotypes, not just a single diagnosis. I think that helped to us to focus the follow-up to the zebrafish studies more broadly and think about how we might test for a relationship between vascular development and eye disease.

AJHG: Thinking about the bigger picture, what implications do you see from this work for the larger human genetics community?

Nancy: I hope that people will begin to think more seriously about using very large-scale phenome information from electronic health records as an adjunct to genetic studies, which we can afford to do in only smaller numbers of individuals. The biobank at Vanderbilt is big — 250,000 subjects, but there are many more (millions) with quality phenome information but no DNA. Finding ways to use both should stretch our ability to make and extend discoveries.

AJHG: What advice do you have for trainees/young scientists?

Nancy: One of my mentors used to remind me on a regular basis that there is no shortage of interesting things to do in science — things that are so interesting they are hard to resist. But only a subset of those things are also important with respect to bigger picture questions or implications for other parts of biology. You have to continually ask yourself whether what you are doing is both interesting and important to insure that you are able to continue, and be funded, to do research that you find irresistible.

AJHG: And for fun, tell us something about your life outside of the lab.

Nancy: I really love the music scene in Nashville! It is amazingly diverse, and we take advantage of the opportunities to hear great music every chance we get.

Nancy Cox, PhD, is Director, Vanderbilt Genetics Institute; Professor of Medicine, Division of Genetic Medicine; Director, Division of Genetic Medicine; and Mary Phillips Edmonds Gray Professor of Genetics at Vanderbilt University. She was the  ASHG President in 2017