Afterword: CEHG Genetics and Society Symposium 2015

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Founded in 2012, CEHG is a research program that fosters interdisciplinary research. Home to more than 25 faculty and more than 200 grads and postdocs, CEHG bridges the divides between various member labs across Stanford campus.

The 2015 CEHG Genetics and Society Symposium (GSS15), which took place on April 13th and 14th in Stanford’s Paul Brest Hall, was a smashing success. It featured 25 speakers from Stanford campus and the San Francisco Bay academic and scientific industry communities. Approximately 175 Stanford affiliates and non-affiliates came together to celebrate the Center’s spirit of interdisciplinary collaboration and meet with experts in the fields of computational, evolutionary and human genomics This is a significant increase from last year’s 150 attendees!

The Mission:

The Genetics and Society Symposium is integral to CEHG’s mission: it provides postdocs and graduate fellows with the opportunity to share their developing research with faculty advisors and their colleagues, encourages conversation between faculty working in diverse scientific disciplines across campus, and introduces CEHG members to speakers from around the Bay Area and beyond (and vice versa).

The Venue:

As you can see from our photos of the space and catering service, Paul Brest Hall was the perfect home for this year’s two-day symposium. The hall was spacious, the food delicious, the staff hands on, and the outdoor picnic area well suited for our lunch and coffee breaks. We enjoyed the venue so much, in fact, that CEHG staff are currently in the process of booking the space for next year!

The Speakers:

GSS15 featured four brilliant keynote speakers, each distinguished in his/her field of research.

Gene Myers and CEHG Exec Committee members Marc Feldman, Chiara Sabatti, and Carlos Bustamante

Gene Myers and CEHG Exec Committee members Marc Feldman, Chiara Sabatti, and Carlos Bustamante

Founding director of a new Systems Biology Center at the Max-Planck Institute of Molecular Cell Biology and Genetics, Dr. Eugene (Gene) Myers presented his open-sourced research on the resurrection of de novo DNA sequencing. Best known for the development of BLAST, the most widely used tool in bioinformatics and the assembler he developed at Celera that delivered the fly, human, and mouse genomes in a three-year period, Dr. Myers participated in GSS15, courtesy of DNAnexus. Follow his blog: https://github.com/thegenemyers.

Co-founding director Carlos Bustamante and Ed Green catch up during a break at GSS15.

Co-founding director Carlos Bustamante and Ed Green catch up during a break at GSS15.

Assistant Professor in Biomolecular Engineering at the University of California, Santa Cruz, Richard (Ed) Green presented his research on a novel approach for highly contiguous genome assemblies, which draws on his work as an NSF Fellow at the Max Planck Institute in Leipzig, Germany and head of an analysis consortium responsible for publishing the draft genome sequence of Neanderthal. Click here for his 2014 CARTA talk, “The Genetics of Humanness: The Neanderthal and Denisovan Genomes.

Dr. Michelle Mello, Stanford Law School and School of Medicine

Dr. Michelle Mello, Stanford Law School and School of Medicine

Michelle Mello, Professor of Law at Stanford Law School and Professor of Health Research and Policy in Stanford’s School of Medicine, presented findings from her extensive research on the ethics of data sharing. As the author of more than 140 articles and book chapters on the medical malpractice system, medical errors and patient safety, public health law, research ethics, the obesity epidemic, and pharmaceuticals, Dr. Mello provided a valuable perspective from the intersections of law, ethics, and health policy. Click here to read Dr. Mello’s SLS profile.

Dr. Ami Bhatt, Stanford Medicine

Dr. Ami Bhatt, Stanford Medicine

Ami Bhatt shared her passion for improving outcomes for patients with hematological malignancies in her talk, “Bugs, drugs, and cancer.” Best known for her recent work demonstrating the discovery of a novel bacterium using sequence-based analysis of a diseased human tissue, her research has been presented nationally and internationally and published in 2013 in the New England Journal of Medicine. Click here for links to Dr. Bhatt’s CAP profile and lab homepage.

 

We had a large group of CEHG faculty members at this year’s event, showcasing the cutting edge research being done in CEHG labs across Stanford campus and indicating considerable faculty commitment to ensuring the Center’s continuing success.

Our symposium would not be complete without our invited CEHG Fellows. These speakers were nominated by organizing committee members to present on topics relating to their CEHG-funded research projects. These young scholars embody CEHG’s continuing commitment to provide funding support to researchers as they transition from graduate studies to postdoctoral scholarships.

The Workshop:

There was standing room only when facilitators Chiara Sabatti (Associate Professor of Health Research and Policy at Stanford), Ken Lange (Chair of the Human Genetics Department at UCLA), and Suyash Shringarpure (postdoctoral scholar in Stanford’s Bustamante Lab) presented their approaches to contemporary problems in statistical genetics!

Social Media:

Did you know? CEHG is on social media!

GSS15 social media moderators, Bridget Algee-Hewitt, Jeremy Hsu, Katie Kanagawa, and Rajiv McCoy were posting live throughout both days of the event. And our efforts to reach the larger community paid off, with a total reach of 815 on Facebook and more than 7,000 impressions on Twitter!

To catch up on our GSS15 coverage, check out our Facebook page at https://www.facebook.com/StanfordCEHG?ref=hl and our Twitter feed @StanfordCEHG. Follow both to make sure you are the first to know when we post CEHG-related news and announcements.

Want to know when speaker videos from the symposium will be available on CEHG’s forthcoming youtube channel? Follow us on Facebook and Twitter!

Special Thanks:

From left to right: Bridget Algee-Hewitt, Cody Sam, Yang Li, Anand Bhaskar, and Katie Kanagawa

From left to right: Bridget Algee-Hewitt, Cody Sam, Yang Li, Anand Bhaskar, and Katie Kanagawa

The GSS15 organizing committee—including Bridget Algee-Hewitt, Anand Bhaskar, Katie Kanagawa, Yang Li, and Cody Sam—would like to take this opportunity to thank CEHG Directors Carlos Bustamante and Marc Feldman, Executive Committee members Hank Greely, Dmitri Petrov, Noah Rosenberg, and Chiara Sabatti, event volunteers Alex Adams, Maude David, and Chris Gignoux, event photographer Deneb Semprum, and everyone who attended this year’s symposium.

We hope you enjoyed attending as much as we enjoyed working behind-the-scenes. We hope to see you all again at GSS16! If you are interested in volunteering for future CEHG events, please contact us at stanfordcehg@stanford.edu.

Upcoming CEHG events:

Don’t miss our popular weekly Evolgenome seminar series, which will continue through Spring term, usually on Wednesdays at noon (location varies). Lunch is always provided. Details will follow, but here is a quick overview so you can mark your calendars!

April 29: Fernando Racimo (Nielsen/Slatkin Lab)
May 6: Pleuni Pennings (UCSF)
May 20: Kelly Harkin
June 3: Sandeep Ventakaram (Petrov Lab)
June 10: Emilia Huerta-Sanchez

How recombination and changing environments affect new mutations

Blog author: David Lawrie was a graduate student in Dmitri Petrov’s lab. He is now a postdoc at USC.

I recently sat down with Oana Carja, a graduate student with Marc Feldman, to discuss her paper published in the journal of Theoretical Population Biology entitled “Evolution with stochastic fitnesses: A role for recombination”. In it, the authors Oana Carja, Uri Liberman, and Marcus Feldman explore when a new mutation can invade an infinite, randomly mating population that experiences temporal fluctuations in selection.

The one locus case

This work builds off of previous research in the field on how the fluctuations in fitness over time (i.e., increased variance of fitness) affect the invasion dynamics of a mutation at a single locus. For a single locus, it has been shown that the geometric mean of the fitness of the allele over time determines the ability of an allele to invade a population. This effect is known as the geometric mean principle. Fluctuations in fitness increase the variance and therefore decrease the geometric mean fitness. The variance of the fitness of the allele over time thus greatly impacts the ability of that allele to invade a population.

What if there are two loci?

In investigating a two locus model, the researchers split the loci by their effect on the temporally-varying fitness: one locus only affects the mean, while the other controls the variance. The authors demonstrate through theory and simulation that:

1)    allowing for recombination between the two loci increases the threshold for the combined fitness of the two mutant alleles to invade the population beyond the geometric mean (see figure).

2)    periodic oscillations in the fitness of the alleles over time lead to higher fitness thresholds for invasion over completely random fluctuations (see figure).

3)    edge case scenarios allow for the maintenance of polymorphisms in the population despite clear selective advantages of a subset of allelic combinations.

Temporally changing environments and recombination thus make it overall more difficult for new alleles to invade a population.

Invasibility thresholds as a function of recombination rate. Recombination makes it more difficult for new alleles to invade a population.

Invasibility thresholds as a function of recombination rate. If there is no recombination (the left-most edge of the figure), the geometric mean of the pair of new alleles needs to be higher than 0.5 to allow for invasion, because the resident alleles’ geometric mean fitness is set to 0.5. However, as recombination between the two loci increases, the geometric mean needed for invasion increases rapidly. If there is free recombination (r = 0.5) then  invasion can only happen if the new alleles’ geometric mean fitness is twice the resident alleles’ geometric mean fitness (light grey area). If the environment is changing periodically, it is even harder for new alleles to invade a population (dark grey area).

The evolution of models of evolution

This work is important for addressing the evolutionary dynamics of loci controlling phenotypic variance – in this case, controlling the ability of a phenotype to maintain its fitness even if the environment is variable. Most environments undergo significant temporal shifts from the simple changing of the seasons to larger scale weather changes such as El Niño and climate change, in which species must survive and thrive. For organisms in the wild, many alleles that confer a benefit in one environment will be deleterious when the environment and selective pressures change. There may be modifier-loci which buffer the fitness of those loci in the face of changing environments. Such modifier-loci have been recently found in GWAS studies and may be important for overall phenotypic variance. Thus modeling the patterns of evolution for multiple loci in temporarily varying environments is a key component to advancing our understanding of the patterns found in nature.

Future work

Epigenetic modifiers are a hot area of research and one potential biological mechanism to control phenotypic variance. The evolution of such epigenetic regulation is a particular research interest of Oana. Future work will continue to explore the evolutionary dynamics of epigenetic regulation and focus on applying the above results to finite populations.

Paper author: Oana Carja is a graduate student with Marc Feldman

Reference

Oana Carja, Uri Liberman, Marcus W. Feldman, Evolution with stochastic fitnesses: A role for recombination, Theoretical Population Biology, Volume 86, June 2013, Pages 29-42, ISSN 0040-5809.