How do different organs and tissues arise? What are the genetic and epigenetic mechanisms that drive this development? To address these questions we design statistical methods and algorithms and apply them to large-scale, genome-wide data. Ultimately, our goal is to generate, test, and confirm hypotheses that are relevant to human health. Current projects include:

Methods for biology at single cell resolution

Over the last several years single cell technologies, predominantly single cell RNA sequencing (scRNA-seq), have become the assay of choice to address questions about cellular heterogeneity, differentiation, and more. However, these new technologies are not without experimental and analytical challenges. Therefore, to better leverage their data, improved general computational methods are needed and custom-tailored analysis approaches are often necessary.
  • scds: Computational Annotation of Doublets in Single Cell RNA Sequencing Data. AS Bais and D Kostka Bioinformatics 2019 (epub ahead of print). ( doi )
  • Random forest based similarity learning for single cell RNA sequencing data. MB Pouyan and D Kostka. Bioinformatics 2018, 34(13):i79-i88. ( doi )

Disease-specific genetic variant prioritization through non-coding regulatory loci

Genome-wide association studies (GWAS) have revealed that the majority of disease-associated genetic variants are in the parts of our genomes that do not encode proteins. Many of these variants fall within gene-regulatory loci that are part of the circuitry determining gene expression. Integrative study of genetic data together with such elements therefore can help prioritize follow-up studies (fine-mapping) and enables informed hypothesis generation about disease mechanism.
  • Genome-wide Enhancer Maps Differ Significantly in Genomic Distribution, Evolution, and Function. ML Benton, SC Talipineni, D Kostka, JA Capra. BMC Genomics 2019, 20(1):511. ( doi )

Embryonic development of heart and kidney

Two of our foci are heart and kidney development. With respect to kidney development, we are interested in nephron progenitor cells (cells that eventually differentiate into all functional components of the nephron), and specifically in their regulation of self-renewal vs. differentiation during development. This is joint work with Dr. Jackie Ho.

In the context of heart development, we are interested in the etiology of congenital heart disease, which is intimately tied to the establishment of left-right symmetry during embryogenesis (the heart is the first left-right asymmetric organ to develop). This is joint work with Dr. Cecilia Lo.

  • Small non-coding RNA expression in developing mouse nephron progenitor cells. YL Phua, A Clugston, KH Chen, D Kostka, J Ho. Scientific Data 2018, Article number: 180218. ( doi )
  • The complex genetics of hypoplastic left heart syndrome. X Liu, H Yagi, S Saeed, AS Bais, GC Gabriel, Z Chen, KA Peterson, Y Li, MC Schwartz, WT Reynolds, M Saydmohammed, B Gibbs, Y Wu, W Devine, B Chatterjee, NT Klena, D Kostka, KL de Mesy Bentley, MK Ganapathiraju, P Dexheimer, L Leatherbury, O Khalifa, A Bhagat, M Zahid, W Pu, S Watkins, P Grossfeld, S Murray, GA Porter Jr, M Tsang, LJ Martin, DW Benson, BJ Aronow, CW Lo. Nature Genetics 2017, 49(7):1152-1159. ( doi )