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.

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.

AAAS 2019: Science Transcending Boundaries

Posted by: Eve Granatosky, PhD, 2018-19 Genetics & Public Policy Fellow

Earlier this month, I attended the Annual Meeting of the American Association for the Advancement of Science (AAAS), held right here in Washington, DC. Themed ‘Science Transcending Boundaries,’ the program featured sessions on how science can bring together people, ideas, and solutions from different disciplines and sectors to address the world’s most pressing problems. This conference was very different from others I’ve attended in the past, which have focused on one specific scientific area. The AAAS Meeting also had a strong focus on science policy and communication, and I was excited to attend those sessions as well as explore scientific talks in different areas.

A common theme across the policy and communication sessions was the importance of understanding your audience – what are their priorities, and what information is valuable and relevant to them? At one session, panelists discussed the many legitimate influences on policy and policymakers, and how scientific evidence is usually only one factor that contributes to decision making. In another, panelists spoke about the challenges of getting usable scientific information to policymakers, and described the important role of boundary organizations that span the science-policy interface in facilitating effective two-way communication. Later on in the conference, panelists discussed how science is frequently used strategically rather than substantively in policy (i.e. to support an existing position rather than develop that position).

The final session of the conference brought many of these ideas together. In “Science Activation: How Do We Get Our Science Used by Those in Power?”, seismologist Lucy Jones reflected on her experience in successfully working with local government and private industry in Los Angeles to better prepare the city for future earthquakes. Her tips and lessons included:

  • Scientists and non-scientists have different communication styles, and scientists’ emphasis on uncertainty can hinder effective communication.
  • Use scientific information to reduce uncertainty whenever possible, by focusing on describing future scenarios based on scientific consensus rather than the probabilities of potential outcomes.
  • Provide policymakers with actionable information to empower them to make decisions, and maintain relationships with stakeholders throughout the process.
At the final session of the AAAS Annual Meeting, Lucy Jones, PhD, and AAAS President Margaret Hamburg, MD, discussed how human stories help engage the public on scientific issues.

Another policy-related highlight of the meeting was an appearance by Kelvin Droegemeier, PhD, the newly confirmed head of the White House Office on Science and Technology Policy. In his first public speech since assuming this position, he highlighted the progress made in science and technology during the Trump administration, including advances in artificial intelligence, quantum sciences, 5G networks, and manufacturing. He also emphasized the role of the private sector in supporting basic research, and the value of assessing all work being done in our country’s research ecosystem, including research in the academic, industrial, nonprofit, and federal agency sectors. By leveraging the strengths of each sector to build new public-private partnerships, he hopes to usher in a “second bold era” of science in the United States. Finally, Dr. Droegemeier acknowledged the need to create safe, welcoming, and accommodating environments for research, as well as to reduce administrative burden for scientists.

The need to improve the climate within science was also addressed at a session entitled “Societies Combatting Sexual Harassment in STEMM Fields,” which formally introduced the Societies Consortium on Sexual Harassment in STEMM. This group of almost 60 scientific societies (including ASHG!) plans to develop resources and guidance to address sexual and gender harassment in all its forms, in both society-organized operations like conferences and broadly within the societies’ scientific fields.

Between all of this excellent policy programming, I attended some great scientific sessions as well, on topics ranging from vaccine development to space exploration. Genetics was best represented at a session entitled “Race, Sex, and Genes: Shaping Bodies, Shifting Boundaries, Challenging Myths,” which delved into how social and biological factors intertwine to contribute to health disparities. Panelists discussed how human genetic variation does exist, but is distributed more geographically and as a gradient than on the strict racial lines dictated by society. They also discussed the complexities of consumer genetic tests in relation to group identity, saying that these tests can be valuable for marginalized people looking to reconnect to their ancestral communities, but should not be used to claim group membership.

Overall, I really enjoyed my time at AAAS 2019! I would highly recommend future editions of this conference for anyone who is interested in science policy and communication, or who is interested in expanding their scientific horizons and learning about new topics.

Eve Granatosky, PhD, is the 2018-19 ASHG/NHGRI Genetics & Public Policy Fellow. She is currently in her second rotation in the United States Congress, working on health and education issues for Senator Richard Blumenthal. Interested in this fellowship? Applications will open in late February.

Biology of Genomes 2018: The Past and Future of Genomics

Posted By: Emily C. Glassberg, PhD Candidate, ASHG Communications Committee

A few weeks ago, I attended the 31st annual Biology of Genomes (BoG) meeting at Cold Spring Harbor. In addition to highlighting the amazing research that comprises the current state of genomics, this meeting highlighted the storied past and bright future of the field. The enthusiastic participation of attendees, both at the meeting and on Twitter, shows incredible energy and momentum as we try to understand the genome’s role in biology, evolution, and disease.

Attendees network at Biology of Genomes 2018 (Credit: Constance Brukin; copyright CSHL)

Genomics Present

The seven scientific sessions covered functional genomics, medical genomics, computational genomics, and evolutionary genomics, as well as genome engineering. Seeing this varied body of work at a single meeting clearly demonstrates that theory, experiment, high-throughput screening, and countless forms of new technology and data analysis all play central roles in shaping our current understanding of the human genome.

And, while the human genome was the primary subject of study, non-human genomes got coverage as well. Highlighted research included the genomes of near relatives, like Neanderthals; to those of best friends, like dogs; to those of model organisms, like yeast. Crowd favorites included Jaemin Kim’s and Elaine Ostrander’s talks using dogs as a system to learn about the genetic basis of complex traits (for the science as well as the adorable pictures).

The scientific programming also included two keynote speakers, Wendy Bickmore and David Page. Bickmore discussed her group’s work on how 3D chromatin structure relates to the mechanism by which enhancers – particularly long-range enhancers – interact with promoters to regulate gene expression.

Bickmore’s emphasis on the need to assay enhancer function in vivo was echoed elsewhere at the meeting. In particular, Emma Farley spoke about high-throughput measurements of enhancer function in the model chordate Ciona. In combination, these talks sparked a conversation about whether current computational models are looking in the wrong places when it comes to predicting enhancer activity and specificity.

Page presented his group’s work on the evolution of sex chromosomes with an eye to understanding sex differences in health and disease. Page’s question of whether and how males and females “read their genomes differently” connected to broader questions that recurred throughout this year’s meeting –  how do we understand the genome dynamically? When and how does the same genome lead to different outcomes?

The ways in which the genome and its downstream effects change over time and space is a big open question, and this year’s BoG showcased many approaches to tackling it:

  • Ben Strober and Jonathan Griffiths both used time-course gene expression data to track how gene regulation changes throughout cellular differentiation and development.
  • Jake Yeung shared an example of dynamic chromatin interactions and rhythmic promoter-enhancer contacts that are connected to circadian rhythm.
  • Christina Leslie presented work on how the chromatin state of tumor specific T-cells changes during cancer progression and how that influences disease treatability.

And that’s just a sample of the exciting work in this space! While we don’t yet have clear answers to these questions, the research discussed at BoG reveals a landscape that is complex, nuanced, and fascinating. What a great time to be in genomics!

Genomics Past

In addition to discussions spanning the range of the current field of genomics, BoG included a brief talk in memoriam of molecular and developmental geneticist John Sulston, who passed away on March 6, 2018. Dr. Sulston was well known for his seminal work in the now-model organism C. elegans, as well as his role in the Human Genome Project. Eric Lander also toasted Jim Watson for his role in the Human Genome Project, and to celebrate his 90th birthday. Lander and other BoG organizers later apologized for the toast, as it was seen by many in the community as minimizing Watson’s history of racist and sexist commentary.

Genomics Future

And, finally, no meeting would be complete without a vision for the future of the field.

A panel on the Ethical, Legal, and Social Implications of genomics research included four perspectives on the promises and pitfalls of germline genome editing. While there is considerable excitement around using CRISPR to cure genetic disease, many issues remain regarding proof of safety as well as ensuring equal access to the technology. Following a lively discussion during the question-and-answer, the consensus seemed to be that germline genome editing is a distant future. In the meantime, we can focus on the application of currently available options, like genetic screening and assisted reproductive technologies.

The National Human Genome Research Institute (NHGRI) also engaged researchers in its current strategic planning initiative, which began in February 2018 and will be completed in 2020. NHGRI is collecting input on priority areas to help the institute live up to its mantra, The Forefront of Genomics.

Of course, the scientific discourse at Biology of Genomes isn’t limited to the talks. The three lively poster sessions were great opportunities to exchange ideas. And many spirited discussions took place during the coffee breaks, over the traditional Cold Spring Harbor banquet, and down at Blackford bar. All told, there’s a lot to look forward in genomics!

Emily C. Glassberg is a PhD Candidate in the Department of Biology at Stanford University. She serves on ASHG’s Communications Committee and has been an ASHG member since 2014.

Advances in the Genetics of Alzheimer’s Disease at AAIC 2017

Posted By: Timothy J. Hohman, Assistant Professor of Neurology, Vanderbilt Memory & Alzheimer’s Center

I just returned from the Alzheimer’s Association International Conference (AAIC) in London. AAIC always covers an amazing breadth of the most recent advances in research and clinical care for Alzheimer’s Disease (AD), and this year placed a particular emphasis on biomarkers. More specifically, the focus was on how we can integrate the growing availability of in vivo biomarkers of AD neuropathology into diagnostic criteria for research, and into screening procedures for clinical trials.

Timothy J. Hohman, PhD (courtesy Dr. Hohman)

The Potential of Biomarkers

Philip Scheltens, MD, PhD, from the VU University Medical Center in the Netherlands kicked off the meeting with an impassioned lecture on the present landscape of biomarkers in AD, and the future potential of biomarkers in screening, diagnosis, targeted treatments, and disease prevention. AD is characterized by two primary neuropathologies: extracellular plaques composed of the amyloid-β protein and neurofibrillary tangles composed of hyper-phosphorylated tau. Over the past ten years, there has been a growing emphasis on measuring these proteinopathies in vivo, including the development of positron emission tomography tracers for amyloid and tau, and the development of assays to measure these proteins in cerebrospinal fluid. In 2011, the National Institute on Aging and the Alzheimer’s Association convened four work groups to develop new research criteria for diagnosis that integrated biomarkers of amyloid deposition into the clinical criteria for dementia. This year’s conversations focused on taking steps towards diagnosis and screening that relied solely on biomarkers.

Dr. Schelten’s emphasis on the future of biomarkers set up a somewhat heated panel presentation laying out a new NIA-AA research framework to investigate Alzheimer’s disease. Led by Clifford Jack, MD, the proposed framework would place a greater emphasis on biomarkers of the two primary proteinopathies, while also emphasizing the measurement and characterization of neurodegeneration. The panel has provided the opportunity for the community to give feedback directly to the workgroup as they continue to refine the proposed framework. Certainly, this will be a critical issue in AD research in the coming year and has important implications for clinical trials, study design, and (eventually) clinical care.

Functional Pathways, GWAS Findings, and AD

This is a genetics blog, though, so let’s get into the genetics! The primary keynote session on the genetics of AD was given by Julie Williams, PhD, from Cardiff University. Dr. Williams provided an overview of where we currently stand in unraveling the genetic architecture of the disease, and called for an increased emphasis on uncovering functional pathways that underlie the known risk loci. Dr. Williams argued the innate immunity and inflammation are fundamental pathways in AD pathogenesis, and that the causal pathways of sporadic AD may be fundamentally distinct from familial forms that operate strictly through an amyloid pathway.

Research presented throughout the conference re-emphasized the importance of innate immunity, including new risk loci in common variant and rare variant analyses completed by the Alzheimer’s Disease Genetics Consortium that implicated innate immune pathways (e.g., LILRA5).  Additionally, many of the functional genomic approaches emphasized the importance of macrophage and monocyte expression in predicting AD, including 14 genes implicated in a genetically regulated transcriptomic analysis by Towfique Raj, PhD, from the Icahn School of Medicine.

Data parasites and data philanthropists both have important roles to play in using big data to study Alzheimer’s. (courtesy Dr. Hohman)

Given the growing emphasis on biomarkers throughout the field of AD, it was also encouraging to see substantial growth in the size of endophenotype analyses, including a GWAS of cerebrospinal fluid biomarkers of AD by Yuetiva Deming, PhD, analyzing data from over 3,000 individuals. Simon Lovestone, PhD, gave an additional “big data” plenary lecture in which he laid out how large-scale European collaborations integrating electronic medical record data and other big data resources will change the way research is completed. He called on #DataParasites (those who perform secondary analyses on existing datasets) to make use of rich data resources to identify new treatment targets and #DataPhilanthropists (data providers) to continue to step up and provide open access to collected data. Large scale data collection, data sharing, and secondary data analysis are becoming central components of AD research.

Varied Approaches to #EndALZ

There were many other areas of focus: from advances in neuroimaging and large-scale omics, to a growing emphasis on sex differences, racial disparities, and pathways of resilience, and a growing acceptance of the heterogeneity in the neuropathological presentation of the disease. If you are interested in AD and want to learn more from a variety of perspectives, this is a fantastic conference to attend. The field of AD is necessarily interdisciplinary and this conference is a fantastic representation of that diversity. Multiple perspectives, approaches, and treatment pathways will be needed to beat this devastating disease. After another year and another great conference, I’m hopeful and inspired to keep working to #EndALZ. Join us!

Timothy J. Hohman, PhD, is an Assistant Professor of Neurology at the Vanderbilt Memory & Alzheimer’s Center. He has been part of the ASHG community since 2013.

An ASHG Fellow’s Perspective on Conference Prep, Part 2: Conference Events

Posted by: Teresa Ramírez, PhD, 2016-17 ASHG/NHGRI Genetics & Education Fellow

See Part 1 of Teresa’s guide, which focuses on networking

Conferences offer a variety of networking events you should fully take advantage of, but keep in mind that scientific sessions and visiting the exhibit hall can also provide new opportunities.

Before attending a conference, it is always a good idea to glance at the agenda and mark workshops of interest. Identify speakers whom you would like to meet. Each conference is unique because each offers various workshops, resources for different career levels, and receptions that allow you to network in a safe space. There is no need to feel shy or stay quiet at a conference; you can always ask questions. Use this time to explore, learn, listen, and communicate.

Use Presenting as an Opportunity

Each conference I’ve attended has provided me with great opportunities that I would have never imagined. I have learned to feel more confident while presenting my research. Was I nervous? Of course, but the more I practiced, the more comfortable I felt. Constructive feedback from people who visited my posters or talks has helped me improve my presentation skills. I was asked questions that provided me with great ideas about what to do next in my research project.

Teresa Ramírez presents her research at the 2017 Japan-NIH Joint Symposium on Advances in Biomedical Research (courtesy Dr. Ramírez)

Presenting a poster or an oral presentation at a conference can also be a good way to interact with people at various career levels, which may lead you to discover similar interests. Be ready with your elevator pitch about your research (a minute or two) and your own branding statement (a simple statement). No need to be arrogant but in simple terms, describe who you are and your interests.

Remember the Exhibit Hall

Most conferences have an exhibit hall with vendors, institutions, resources, and career centers. Take advantage and visit them. This can help improve your networking skills or spark ideas for the next step of your career. By strolling around conference exhibit halls, I have learned about summer internships, scholarships, fellowships, post-baccalaureate programs, and graduate schools. Now, I learn about new job opportunities or professional/leadership training opportunities.

Relax and Enjoy the Experience

You never know whom you will meet or what you can learn from a conversation with a stranger. So make sure you have a plan but also go with the flow and enjoy every minute of your conference experience. Don’t stress about it. At conferences, I have met people who became life time friends and wonderful mentors who have been instrumental in my career through their advice and support.

Please check out the ASHG website for more information on trainee opportunities, resources, and ASHG 2017.

Teresa Ramírez, PhD, is the 2016-2017 ASHG/NHGRI Genetics & Education Fellow. Learn more about the Genetics & Education Fellowship.

An ASHG Fellow’s Perspective on Conference Prep, Part 1: Networking

Posted by: Teresa Ramírez, PhD, 2016-17 ASHG/NHGRI Genetics & Education Fellow

Attending national conferences can be intimidating or exciting. The first one I attended was quite overwhelming. Do you remember how you felt at yours? Did you ask yourself questions like: why is it important to attend a national conference? How do I prepare? How can I make the most of it? What should I do and how do I network? These thoughts can be nerve-wracking, but don’t worry: these tips will help ease your nerves and guide you to prepare for the next one.

Meet People and Follow Up

As an undergraduate student at California State University, Dominguez Hills, I participated in the NIH-funded Minority Biomedical Research Support (MBRS) program, where I learned about the do’s and don’ts of attending conferences. First, look and dress professionally because first impressions make a difference.

Teresa Ramírez at a recent meeting of SACNAS (Advancing Chicanos/Hispanics & Native Americans in Science) (courtesy Dr. Ramírez)

Second, be sure to have business cards. It might seem outdated, but business cards can help break the ice and start conversations. I know that reaching out and introducing yourself might be uncomfortable, but it will all be worthwhile even if you end up feeling dead tired and drained. Make sure your business cards include your full name, degree/title, organization, contact information, LinkedIn URL, and something that can grab people’s attention in a positive way. One of my tips is to immediately write on the back of each card collected the date you met that person, key words to help you remember the conversation, and the name of the event/location. These notes are helpful because, believe it or not, you will start collecting tons of cards and by the end of the day, you will forget which card belongs to whom. Nurture these new relationships by writing follow up emails; showing interest and professionalism can set you apart.

In 2016, Dr. Ramírez presented on STEM careers to a group of high school interns, a talk she was invited to give by a contact whom she met at a dinner. (courtesy Dr. Ramírez)

By networking, you never know who you can meet and what the outcome can be. You can meet your next mentor, find out about a new opportunity, or start a new collaboration. You might even get invited to do a research talk or share your story with K-16 students, like I did. Keep reminding yourself to be open-minded and network with new people during meals. Attendees usually feel comfortable sitting with people they know, but this is the right time to try sitting with unfamiliar faces to start a conversation. During this time, you have the opportunity to network, introduce yourself, and even use your scientific elevator pitch. I have sat in tables with total strangers feeling a little uncomfortable at first but at the end, had wonderful conversations and met new friends.

Please check out the ASHG website for more information on trainee opportunities, resources, and ASHG 2017.

Teresa Ramírez, PhD, is the 2016-2017 ASHG/NHGRI Genetics & Education Fellow. Learn more about the Genetics & Education Fellowship.

Teens’ Nuanced Views about Genetic Testing, at ESHG 2017

Posted by: Michael Dougherty, PhD, ASHG Director of Education

What do adolescents think about genetic testing – in particular, clinical recommendations to defer genetic testing for adult-onset conditions? We are beginning to have an answer, thanks to a research collaboration involving ASHG, Geisinger, and Sarah Lawrence College. Late last month, I had the opportunity to present our initial analysis at the 2017 European Human Genetics Conference (ESHG 2017) in Denmark.

Nyhavn waterfront, Copenhagen, Denmark. (Credit: Michael Dougherty)

First, for those who haven’t been to Copenhagen, it’s a beautiful city that I highly recommend. Deep history, friendly people (almost all of whom speak excellent English), and the convenient mass transit that is so typical of Europe. Walk along the canals or climb the external staircase to the top of Vor Frelser’s Kirke (Our Savior’s Church). An hour north of Copenhagen, Kronborg Castle, which is the model for Shakespeare’s Elsinore in Hamlet, is an especially nice day trip. If you’re adventurous, try the Danish national meal, ‘stegt flæsk,’ a delicious crispy pork dish, which came with the following warning in our restaurant’s menu: “Ask your waiter before ordering”! But now, back to the research.

Little is known about how adolescents view genetic testing, especially the psychosocial impacts of the benefits and harms frequently discussed by experts, yet clinical practice often involves decisions that may affect them. Our research used data from ASHG’s annual DNA Day Essay Contest entries to characterize adolescents’ views.

ASHG’s 2016 DNA Day Essay Contest question asked high school students to identify an adult-onset genetic condition and to defend or refute the recommendation in ASHG’s 2015 position statement to defer genetic testing until adulthood. Over 1,200 essays from 45 U.S. states and 22 non-U.S. countries were assessed using thematic, mixed-methods analysis. Students identified 100 conditions, but 75% chose one of five more familiar disorders, including Huntington disease, hereditary breast and ovarian cancer (e.g., BRCA), and Alzheimer’s. Across all conditions, roughly equal numbers of students chose to defer testing as to not defer.

We then dug deeper to examine students’ choices regarding specific conditions, such as testing for a BRCA predisposition to breast and ovarian cancer (BRCA) and for Alzheimer’s disease (AD), which differ considerably in medical actionability. Here some statistically significant differences began to emerge. With AD, nearly two-thirds of students chose to defer testing, whereas with BRCA, fewer than half chose to defer.

The reasons students gave to justify their decisions were sophisticated and often matched those reflected in clinical guidelines and ethical discussions. Reasons to defer often included risk of psychological harm to the minor or the uncertainty of predictions arising from test results (e.g., ApoE4). Reasons not to defer included the benefits of alleviating uncertainty and preparing for increased surveillance (e.g., early, regular mammograms).

The rich data provided in the students’ essays will be mined for additional insights that may inform the development of future recommendations, but even now it appears clear that the decisions of mature adolescents should be taken seriously by clinicians.

Michael J. Dougherty, PhD, is Director of Education at ASHG. This research collaboration’s work was presented at ESHG 2017 as a poster and featured in the meeting’s Best Posters Session.