June 4th, Christine Peterson: Multiple testing procedures for eQTL discovery

Christine Peterson

Christine Peterson

Christine Peterson is a postdoctoral scholar at Stanford working with Chiara Sabatti. Her current research is focused on the development of statistical methods to account for multiple hypothesis testing in the context of multivariate phenotypes. Before coming to Stanford, Christine earned an undergraduate degree in applied mathematics from Harvard and a PhD in statistics from Rice University. Her doctoral research was focused on the inference of biological networks using Bayesian graphical models, including applications to the inference of cellular metabolic networks and protein networks in cancer.

Talk: Multiple testing procedures for eQTL discovery

We are developing methods to both improve power and reduce errors in identifying genetic variants that are relevant to multivariate phenotypes such as imaging features, actigraphy measures, or gene expression. Since both the predictor and response variables are high-dimensional, this represents a massive multiple testing problem. For expression quantitative trait loci (eQTL) studies, which focus on gene expression as the outcome measure, the current standard approach to identify genetic effects is to compute pairwise tests of association for each SNP to its nearby (or cis) genes, then control the false discovery rate across all such tests. The search for distant (or trans) eQTLs is typically run separately and is often underpowered. In this talk, I will discuss improvements to this procedure which allow the integration of cis and trans eQTLs through appropriately chosen weights and which take into account the problem structure by focusing on families of hypotheses based on genomic location. The proposed methods will be illustrated both through simulations and through an application to a study of traits associated with bipolar disorder.

Seminar details

Wednesday June 4th, 2014
1:00 PM Lunch In Clark S360
1:15 PM Seminar
Location: Clark S360

May 28th, Rui Zhang: Evolutionary Analysis Reveals Regulatory and Functional Landscape of RNA Editing

Rui Zhang

Rui Zhang

Rui Zhang is a postdoc in Dr. Jin Billy Li’s lab (2011 – now) in the Department of Genetics, studying the dynamics and evolution of RNA editing. He completed his PhD at Kunming Institute of Zoology, Chinese Academy of Sciences in 2009 with Dr. Bing Su, investigating the miRNA-mediated gene regulatory network. Before moving to Stanford, he worked at Beijing Institute of Genomics with Chung-I Wu, studying the miRNA targeting evolution.

Talk: Evolutionary Analysis Reveals Regulatory and Functional Landscape of RNA Editing

Adenosine-to-inosine RNA editing, catalysed by adenosine deaminases acting on RNA (ADAR), promotes functional diversity and is especially prevalent in neural tissues. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Using the Drosophila genus as a model, we found the establishment of editing and variation in editing levels are largely explained and predicted by cis regulatory element changes. We show that a large fraction of nonsynonymous and 3’UTR editing sites is under evolutionary constraint, highly edited, and thus likely functional. Furthermore, newborn sites are lowly edited and sparsely distributed across genes with diverse functions, while long-lived sites tend to be highly edited in clusters and enriched in slowly-evolved neuronal genes. Our results suggest that RNA editing, rather than nucleotide substitution at the DNA level, may be the preferred evolutionary means of fine-tuning neuronal functions.

Seminar details

Wednesday May 28th, 2014
1:00 PM Lunch In Clark S360
1:15 PM Seminar
Location: Clark S360

May 21st, Iain Mathieson, “Demography and the age of rare variants”

IainMathiesonIain Mathieson is a postdoc in David Reich’s lab at Harvard, working on approaches to detect selection in recent human evolution using ancient DNA. He is spending this semester at the Simons Institute for the Theory of Computing at UC Berkeley. Before moving to Harvard, he completed his PhD at Oxford with Gil McVean, investigating the genetics of spatially structured populations.

Talk: Demography and the age of rare variants.

The distribution of rare variants can be highly informative about recent population history. One way to use this information is to infer the age of these variants using their surrounding haplotype structure. These ages vary enormously. For example, depending on population, the age of variants at frequency 0.1% in the 1,000 Genomes data varies from tens to thousand of generations, revealing the influence of population splits, admixtures and bottlenecks. We can  derive explicit estimators for historical effective population sizes and migration rates by treating these ages as samples from the distribution of coalescent times. This approach is very accurate for the recent past, which makes it a useful complement to sequentially Markovian coalescent approaches which are most accurate for older events.

Seminar details

Wednesday May 21st, 2014
1:00 PM Lunch In Clark S360, (sign up below)
1:15 PM Seminar
Location: Clark S360

 

May 14th, Philip Labo: Yeast population dynamics: Stopping times and logistic curves.

Philip Labo

Philip Labo

IN CLARK S360!!

Philip Labo studied both biology and computer science as an undergraduate at Penn. He received his B.A., in biology, in 2004. During that time he also worked as a programmer/analyst for the Plasmodium falciparum genome database (plasmodb.org). Philip left Penn for Stanford in Fall 2005 to pursue a doctorate in statistics. His doctoral research focused on the modeling of adaptive evolution in certain populations of baker’s yeast. He also studied the modeling of adaptive evolution in general. During the Spring of 2011 he started working with Jamie Jones, of the Stanford Anthropology Department, on the analysis of evolutionary pressures on life history patterns in the Utah Population Database. Philip now works as a post-doctoral scholar with the Prematurity Research Center in the Stanford School of Medicine lending his statistical expertise to the study of preterm birth in United States. Jamie Jones and Paul Wise oversee his work.

Talk: Yeast population dynamics: Stopping times and logistic curves

Kao & Sherlock (2008) describes eight experiments with baker’s yeast. Each experiment involves a chemostat, a sugar-limited medium, a numer- ically large baker’s yeast population, and the evolution of said population over nearly five hundred generations. The output from these experiments lead us to consider the Wright-Fisher and Moran models of population ge- netics lore (Fisher (1922); Wright (1931); Moran (1958)). How might we expect these populations to behave if under the influence of such simple underlying dynamics? We study expected stopping times and expected path functions, reviewing old results and deriving new. We also provide a loose demonstration of our efforts to fit said models to the data from Kao & Sherlock (2008). While these relatively simple models may “fit” these data, this does not suggest that these simple dynamics actually obtain in real life (see for example Desai & Fisher (2007)).

Seminar details

Wednesday May 14th, 2014
1:15 PM Seminar
Location: Clark S360!!

May 7th, Devaki Bhaya: Cooperation and conflict in microbial communities: a molecular view

Devaki Bhaya

Devaki Bhaya

Devaki Bhaya is a professor in the Department of Plant Sciences. “Research in my lab is driven by an interest in understanding how photosynthetic microorganisms perceive and evolve in response to environmental stressors, such as light, nutrients and viral attack. We focus on cyanobacteria which are abundant, globally relevant and have been used to probe environmentally important processes ranging from photosynthesis to symbioses to circadian rhythms. We work both with model organisms and with cyanobacteria in naturally occurring communities.”

Talk: Cooperation and conflict in microbial communities: a molecular view

We know surprisingly little about the activity and co-existence of microbial and viral life in communities. High throughput sequencing and “omics” technologies have allowed us a first tantalizing glimpse into the diversity of this hidden world. I’ll focus on cyanobacteria which are environmentally important and have been used to probe important processes ranging from photosynthesis to symbioses to circadian rhythms. Using techniques ranging from metagenomics to in situ biochemical analyses we have attempted to explore how genomic diversity and metabolic versatility are integrated into microbial community function. I will use examples that highlight our current interests, particularly the way we are using CRISPR Cas based adaptive immunity to explore the conflict and co-evolution of bacteria and viruses. I believe that progress will require both interdisciplinary collaborations and in-depth analysis and look forward to feedback and debate.

Seminar details

Wednesday May 7th, 2014
1:15 PM Seminar (no lunch, but cookies and lemonade afterwards)
Location: Clark Auditorium