Michael F. Lin

Graduate Student
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Research Interests

I work on computational comparative genomics in the lab of Manolis Kellis. Specifically, I am developing methods for the analysis of protein-coding genes in alignments of multiple related genomes. The purpose of these methods is to use evolutionary signatures at the DNA sequence level to (1) validate and revise existing gene annotations; (2) identify novel genes and exons ab initio; and (3) discover unusual genic phenomena, such stop codon readthrough, translational frame-shifting, polycistronic mRNAs, and extremely small proteins.

We are applying these methods to the genomes of several fungal species (including baker's yeast, Saccharomyces cerevisiae, and a human pathogen, Candida albicans), the fruit fly Drosophila melanogaster, and the human, using genome alignments with several related informant species in each case - at last count, seventeen fungi, twelve flies, and twenty-nine mammals. Ultimately, our efforts will help produce the best possible gene annotations for the ever-increasing collection of sequenced genomes.

Publications

• Drosophila 12 Genomes Consortium (2007). Evolution of genes and genomes on the Drosophila phylogeny. Nature 450:203-218.
• Stark A*, Lin MF*, Kheradpour P*, Pedersen JS*, et al. (2007). Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures. Nature 450:219-232.
• Lin MF, Carlson JW, Crosby MA, Matthews BA, et al. (2007). Revisiting the protein-coding gene catalog of Drosophila melanogaster using twelve fly genomes. Genome Research 17:1823-1836.
• Clamp M, Fry B, Kamal M, Xie X, Cuff J, Lin MF, Kellis M, Lindblad-Toh K and Lander ES (2007). Distinguishing protein-coding and noncoding genes in the human genome. Proc Natl Acad Sci USA 104:19428-19433.
• Lin MF, Deoras AN, Rasmussen MD, and Kellis M (2008). Performance and scalability of discriminative metrics for comparative gene identification in 12 Drosophila genomes. PLoS Comput Biol 4:e1000067.
• Guttman M, Amit I, Garber M, French C, et al. (2009). Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 458:223-227.
• Butler G, Rasmussen MD, Lin MF, Santos M, et al. (2009). Evolution of pathogenicity and sexual reproduction in eight Candida genomes. Nature 459:657-662.
• Pruitt KD, Harrow J, Harte RA, Wallin C, et al. (2009). The consensus coding sequence (CCDS) project - identifying a common protein-coding gene set for the human and mouse genomes. Genome Research 19:1316-1323.

Software

• "The Whitespace Thing", a preprocessor for Objective Caml that provides Python/Haskell-like indentation awareness.
• Yaxpo, a reentrant XML parser for OCaml.
• Freeware Windows programs with millions of downloads.