Learning Gene Networks Underlying Clinical Phenotypes Using SNP Perturbations
Friday, November 2nd, 2018 from 12-1 pm in GHC 6501.
Recent technologies are generating an abundance of genome sequence data and molecular and clinical phenotype data, providing an opportunity to understand the genetic architecture and molecular mechanisms underlying diseases. Previous approaches have largely focused on the co-localization of single-nucleotide polymorphisms (SNPs) associated with clinical and expression traits, each identified from genome-wide association studies and expression quantitative trait locus (eQTL) mapping, and thus have provided only limited capabilities for uncovering the molecular mechanisms behind the SNPs influencing clinical phenotypes. Here we aim to extract rich information on the functional role of trait-perturbing SNPs that goes far beyond this simple co-localization. We introduce a computational framework called Perturb-Net for learning the gene network that modulates the influence of SNPs on phenotypes, using SNPs as naturally occurring perturbation of a biological system. Perturb-Net uses a probabilistic graphical model to directly model both the cascade of perturbation from SNPs to the gene network to the phenotype network and the network at each layer of molecular and clinical phenotypes. Perturb-Net learns the entire model by solving a single optimization problem with an extremely fast algorithm that can analyze human genome-wide data within a few hours. In our analysis of asthma data, for a locus that was previously implicated in asthma susceptibility but for which little is known about the molecular mechanism underlying the association, Perturb-Net revealed the gene network modules that mediate the influence of the SNP on asthma phenotypes. Many genes in this network module were well supported in the literature as asthma-related.
The Student Seminar Series is an informal research seminar by and for SCS graduate students from noon to 1 pm on Mondays and Fridays. Lunch is provided by the Computer Science Department (personal thanks to Debbie Cavlovich!). At each meeting, a different student speaker will give an informal, 40-minute talk about his/her research, followed by questions/suggestions/brainstorming. We try to attract people with a diverse set of interests, and encourage speakers to present at a very general, accessible level.
So why are we doing this and why take part? In the best case scenario, this will lead to some interesting cross-disciplinary work among people in different fields and people may get some new ideas about their research. In the worst case scenario, a few people will practice their public speaking and the rest get together for a free lunch.
Note: Step #1 below are applicable to all SSS speakers. You can schedule AT MOST THREE talks per semester.
SSS is an ideal forum for SCS students to give presentations that count toward fulfilling their speaking requirements. The specifics, though, vary with each department. For instance, students in CSD will need to be familiar with the notes in Section 8 of the Ph.D. document and follow the instructions outlined on the Speakers Club homepage. Roughly speaking, these are the steps:
Qing Zheng, CSD