A number of functional genomic tools have recently been made available to the biological research community including gene expression, all exon, genomic tiling, yeast TAG and whole genome SNP microarrays as well as low cost, high throughput sequencing. These new tools allow investigators to study fundamental processes in molecular biology on a genomic scale. My laboratory is focused on developing software tools to analyze and integrate data generated from these various platforms to identify global genome wide trends that address mechanistic hypotheses as well as find biologically interesting genomic targets for further downstream functional validation. We are currently involved in a number of collaborations with molecular biologists at UVA which include identifying drug targets using yeast TAG arrays, understanding the impact of Mot1 and histone variants on transcription using genomic tiling arrays, uncovering the role of alternative splicing in breast cancer cells using all exon arrays and profiling epigenetic and gene expression changes in neural circuits important in behavior and sexual differentiation.

Another major focus of my laboratory is the application of physical models to the process of hybridization with the aims of improving array design and analysis. While at Affymetrix, I worked on precise physical modeling of controlled concentration spike data sets (i.e., targets are spiked in at 14 different pre-determined concentrations in both simple and complex genomic sample backgrounds). Despite significant progress, fundamental mysteries remain. For example, the apparent binding capacity of probes, which should be a constant, varies by 2-3 orders of magnitude. Cross-hybridization of targets to un-intended probes has been observed as spurious signal in gene expression arrays. However, physical models that are capable of predicting the likelihood that a given unintended target will cross-hybridize do not exist. We are working on these problems using spike-in control data sets recently generated at Affymetrix.

Selected References

Park T, Kim Y, Bekiranov S, Lee JK. (2007) "Error-pooling-based statistical methods for identifying novel temporal replication profiles of human chromosomes observed by DNA tiling arrays." Nucleic Acids Res. 35:e69. Epub 2007 Apr 11. [PubMed]

Jeon Y, Bekiranov S, Karnani N, Kapranov P, Ghosh S, MacAlpine D, Lee C, HwangDS, Gingeras TR, Dutta A. (2005) "Temporal profile of replication of human chromosomes." Proc Natl Acad Sci U S A. May 102(18):6419-24. Epub 2005 Apr 21. [PubMed]

Bernstein BE, Kamal M, Lindblad-Toh K, Bekiranov S, Bailey DK, Huebert DJ,McMahon S, Karlsson EK, Kulbokas EJ 3rd, Gingeras TR, Schreiber SL, Lander ES. (2005) "Genomic maps and comparative analysis of histone modifications in human and mouse." Cell. Jan 120:169-81. [PubMed]

Cawley S, Bekiranov S, Ng HH, Kapranov P, Sekinger EA, Kampa D, Piccolboni A,Sementchenko V, Cheng J, Williams AJ, Wheeler R, Wong B, Drenkow J, Yamanaka M,Patel S, Brubaker S, Tammana H, Helt G, Struhl K, Gingeras TR. (2004) "Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs." Cell. Feb 116:499-509. [PubMed]

Mei R, Hubbell E, Bekiranov S, Mittmann M, Christians FC, Shen MM, Lu G, Fang J,Liu WM, Ryder T, Kaplan P, Kulp D, Webster TA. (2003) "Probe selection for high-density oligonucleotide arrays." Proc Natl Acad Sci U S A. Sep 100(20):11237-42. Epub 2003 Sep 19. [PubMed]