Itsik Pe'er - Research

The Pe'er lab is actively reqruiting talented individuals for undergraduate credit projects, programming positions, graduate and prostdoctoral studies. Contact me for details.

Overview

I study, develop and apply novel computational methods in human genetics.

How is it best to measure, describe and quantify differences between individual DNA sequences? How does sequence variation affect biological processes? How can we use it to understand and influence human disease? All these questions pose complex analytical challenges, with direct impact on medical research.

Human genetics is as ancient as human history. It's computational foundations are intertwined with the most fundamental developments in statistics. Such quantifications reveal the tremendous degree to which medical traits are heritable, and motivate a large research community to investigate the interconnections between gene variants (genotypes) and observed traits (phenotypes). The third millenium finds genetics more flourishing than ever with high throughput technologies generating large scale data sets, yet with more need than ever of computational innovation and methods to process these data into meaningful biomedical insights. The upcoming era, of complete genotype information available to each individual on the planet therefore holds the potential of great discoveries, and poses the challenges of powerful and rigorous analyses of these data.


Genetics of special populations

A model system where complete genetics can be practiced at present is a small, isolated population. In such a place everybody can genotyped for the markers along entire genome, and because of the bottleneck effect on gene flow during founding of the population, markers would exhibit high correlation to disease-causing variants, therefore the marker density offered by current technology has the potential of dissecting the genetics of heritable disease.

The Pacific island of Kosrae, Federates States of Micronesia is exatly such a population. Furthermore, high prevalence of the diabetes, obesity, hypertension and hyperlipidemia make the island a compelling population to dissect the genetics of their combination, the Metabolic Syndrome. Joint with Jeff Friedmann's and other labs at the Rockefeller Institute and the Altshuler/Daly group at Broad Institute we have quantified the effects of population isolation in Kosrae, and mapped European admixture into the island. We have recently generated genomewide data for essentially the entire adult population, making an association study for metabolic disorders of unprecedented magnitude and complexity.

We are continually developing computational methods to handle the complexities of the Kosrae data and other special populations in terms of magnitude, population isolation, internal family relatedness, and ethnic admixture.


Predicting variation in the general population

Current technologies allow experimentally typing only a small fraction of human genetic variants. Yet, due to correlation among alleles of nearby markers called Linkage Disequilibrium, we are able to infer the genotypes of other markers in the same samples. We are using data form the Human Haplotype Map (HapMap) to train advanced computational models that predict most of the 10 million human variants based on observing only two orders of magnitude less data points.

Active research projects include


Somatic genetic variation

Cancer is a genetic illness of cells. Somatic lineages suffer loss and gain of parts of the genome. As somatic copy number changes occur randomly, but may be sometimes selected for in tumorgenesis, we are investigating the allele specificity of this selection, i.e., the connections between an individual's germline genotype and the observed copy number changes in the tumor's somatic genotypes.


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