||||Sinha Laboratory

X. He, S. Sinha. (2010). ChIPs and Regulatory Bits. Nature Biotechnology , 28, 142 – 143. [Full Text]

The Nasonia Genome Working Group: Werren, J.H., Richards, S. , … Kim, J., … Sinha, S., … Gibbs, R.A. (157 authors). (2010). Functional and Evolutionary Insights from the Genomes of Three Parasitoid Nasonia Species. Science (2010). Vol. 327. no. 5963, pp. 343 – 348 [IN THE NEWS] [SCIENCE PODCAST] [Pubmed] [Synopsis]

(Taken from Genome Web) “Nasonia Genome Working Group Publishes Results From Three Parasitoid Wasp Genomes: An international research team has sequenced and compared the genomes of three parasitoid wasp species belonging to the genus Nasonia, gaining new insights into the wasps’ biology and evolution. Those involved say genetic and genomic resources generated through the effort will help support the use of Nasonia wasps as model genetic organisms and biocontrol agents.”

J. Kim, R. Cunningham, B. James, S. Wyder, J. D. Gibson, O. Niehuis, E. M. Zdobnov, H. M. Robertson, G. E. Robinson, J. H. Werren, and S. Sinha. (2010). Functional Characterization of Transcription Factor Motifs Using Cross-species Comparison across Large Evolutionary Distances. PLoS Computational Biology 6(1): e1000652. doi:10.1371/journal.pcbi.1000652. [Synopsis] [Full Text]

This is our companion paper to the Nasonia genome paper published in Science magazine. We develop a computational pipeline for predicting the functions of transcription factor motifs, through DNA sequence analysis. The pipeline is applied to the newly sequenced genome of the jewel wasp, Nasonia vitripennis. It exploits the wealth of molecular data available in another insect species, the fruitfly Drosophila melanogaster, and uses cross-species comparison to its advantage. Our main contribution is to show how this can be done despite the large evolutionary divergence between the two species. The methodology presented here may be applied more generally to other scenarios (genomes) where comparative regulatory genomics must deal with large evolutionary divergences.

J. Kim, S. Sinha (2010). Towards realistic benchmarks for multiple alignments of non-coding sequences. BMC Bioinformatics. In press.

S. Sinha, X. He. (2010). [Invited Book Chapter] Evolution of regulatory sequences in Drosophila species. Computational Biology of Transcription Factor Binding: Methods and Protocols. Ed: Istvan Ladunga. Humana Press. In press.

X. He, F. Hong, C. Chen, F. Fang, S. Sinha, H. Ng, S. Zhong. (2009). Predicting combinatorial protein-DNA interactions from sequences and ChIP-seq data using biophysical modeling. RECOMB Regulatory Genomics 2009. PloS one 2009;4(12):e8155.[Pubmed]

A. Moses and S. Sinha. (2009). [Invited Book Chapter] Regulatory Motif Analysis. Bioinformatics; Tools and Applications. Ed: David Edwards, Jason Stajich, David Hansen. Springer.

M.R. Kantorovitz, M. Kazemian, S. Kinston, D. Miranda-Saavedra, Q. Zhu, G.E. Robinson, B. Gottgens, M.S. Halfon, S. Sinha. (2009). Motif-blind, genome-wide discovery of cis-regulatory modules in Drosophila and mouse. Developmental Cell, Volume 17, Issue 4. [IN THE NEWS] [Pubmed] [Synopsis]

This paper presents a computational method to discover cis-regulatory sequences (enhancers) in a genome without knowledge of transcription factor motifs. The method is shown to be effective in insect as well as mammalian genomes. It is especially useful for investigation of gene regulatory networks with relatively little prior characterization.

C. Alaux, S. Sinha, L. Hasadsri, G.J. Hunt, E. Guzman-Novoa, G. DeGrandi-Hoffman, J.L. Uribe-Rubio, B.R. Southey, S. Rodriguez-Zas, and G.E. Robinson. (2009). Honey bee aggression supports a link between gene regulation and behavioral evolution. Proc. Natl. Acad. Sci, 106, 15400-15405. [IN THE NEWS] [Pubmed] [Partial Synopsis]
We used motif scanning in the honeybee genome to associate particular transcription factor motifs with the regulation of aggression-related genes. Working independently on genes whose brain expression distinguishes the European honeybee from the more aggressive Africanized honeybee, genes whose expression distinguished young honeybees from the more aggressive older adults, and genes that responded to alarm pheromone (which provokes aggression), we found the same cis-regulatory controls showing up in each of these three cases. A rigorous estimate of the statistical significance of this observation was part of a comprehensive study that shows a link between gene regulation and evolution of behavioral traits.

A. Kumarasubramanian R. Venkatesan, S. Sinha. (2009). MalDiff: Control Flow Mutations and Malware Detection. Malware 09, Quebec, Montreal. (Accepted.)

C. Alaux, Y. Le Conte, H. Adams, S. Rodriguez-Zas, C. Grozinger, S. Sinha, G.E. Robinson. (2009). Regulation of Brain Gene Expression in Honey Bees by Brood Pheromone Genes, Brain and Behavior , 8(3):309-19. [Pubmed]

J. Kim, X. He, S. Sinha (2009). Evolution of Regulatory Sequences in 12 Drosophila Species. PLoS Genetics, 5(1):e1000330. [Pubmed]

X. He, X. Ling, S. Sinha (2009). Alignment and Prediction of cis-Regulatory Modules Based on a Probabilistic Model of Evolution. PLoS Computational Biology, 5(3):e1000299. [Pubmed]

A. Kosorukoff, S. Sinha (2008). Heart of the Matter: discovering the consensus of multiple clustering results. Proc. of the IEEE International Conference on Bioinformatics and Biomedicine, Philadelphia.

A. Ivan, M.S. Halfon, S. Sinha (2008). Computational discovery of cis-regulatory modules in Drosophila, without prior knowledge of motifs. Genome Biology. 9(1):R22. (Marked by journal as highly accessed.) [Pubmed]

M.B. Noyes, X. Meng, A. Wakabayashi, S. Sinha, M.H. Brodsky, S.A. Wolfe (2008). The systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Res. 36, 2547-2560. [Pubmed]

S. Sinha, A.S. Adler, Y. Field, H.Y. Chang, E. Segal (2008). Systematic Functional Characterization of cis-Regulatory Motifs in Human Core Promoters. Genome Research. 18:477-488. [Pubmed]

S. Sinha and X. He (2007). MORPH: Probabilistic alignment combined with Hidden Markov Models of cis-regulatory modules. PLoS Computational Biology. 3(11):e216. [Pubmed]

A. Adler, S. Sinha, E. Segal, H. Chang. (2007). Motif module map reveals enforcement of aging by continual NF-kB activity. Genes & Development, 21:3244-3257. Cover article. Recommended by Faculty of 1000. [Pubmed]

L. Li, Q. Zhu, X. He, S. Sinha and M.S. Halfon. (2007) Large-scale analysis of transcriptional cis-regulatory modules reveals both common features and distinct subclasses. Genome Biology 8, R101. (Marked by journal as highly accessed.) [Pubmed]

R. Kantorovitz, G. E. Robinson and S. Sinha (2007).  A statistical method for alignment-free comparison of regulatory sequences. Bioinformatics, 23(13). (Special Issue on ISMB 2007). (Acceptance rate: 15% in over 400.) [Pubmed]

J. Kim and S. Sinha (2007) Indelign: a probabilistic framework for annotation of insertions and deletions in a multiple alignment. Bioinformatics, 23(3). [Pubmed]

S. Sinha (2007). [Invited Book Chapter] PhyME: a software tool for finding motifs in sets of orthologous sequences. Methods Mol Biol.;395:309-18. [Pubmed]

S. Sinha, X. Ling, C.W. Whitfield, C. Zhai, G.E. Robinson (2006) Genome scan forcis-regulatory DNA motifs associated with social behavior in honey bees. Proc. Nat. Acad. Sciences, 103(44). [Pubmed]

S. Sinha (2006). On counting position weight matrix matches in a sequence, with application to discriminative motif finding. Bioinformatics, 22(14). (Special Issue on ISMB 2006). (Acceptance rate: 15% in over 400.) [Pubmed]

S. Sinha, Y. Liang, E.D. Siggia (2006). Stubb: a program for discovery and analysis of cis-regulatory modules. Nucl. Acids Res, 34 (Web server issue): W555-9. [Pubmed]

S. Sinha and E. D. Siggia (2005). Sequence Turnover and Tandem Repeats in cis-Regulatory Modules in Drosophila. Molecular Biology and Evolution, 22(4):874-85. [Pubmed]

M. Tompa, N. Li, T. L. Bailey, G. M. Church, B. DeMoor, E. Eskin, A. V. Favorov,  M. C. Frith, Y. Fu, W. J. Kent, V. J. Makeev, A. A. Mironov, W. S. Noble, G. Pavesi, G. Pesole, M. Regnier, N. Simonis, S. Sinha, G. Thijs, J. van Helden, M. Vandenbogaert, Z. Weng, C. Workman, C. Ye, Z. Zhu. (2005) An Assessment of Computational Tools for the Discovery of Transcription Factor Binding Sites,Nature Biotechnology, Vol. 23, No. 1, pp. 137 – 144. [Pubmed]

S. Sinha, M. Blanchette, and M. Tompa (2004). PhyME: A Probabilistic Algorithm for Finding Motifs in Sets of Orthologous Sequences. BMC Bioinformatics, 5(170). (Marked by journal as Research Highlight.) [Pubmed]

S. Sinha, M. Schroeder, U. Unnerstall, U. Gaul, and E. D. Siggia (2004). Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila. BMC Bioinformatics, 5(129). Cited by the Faculty of 1000. [Pubmed]

A. Prakash, M. Blanchette, S. Sinha, M. Tompa (2004). Motif Discovery in Heterogeneous Sequence Data, Ninth Pacific Symposium on Biocomputing (PSB). [Pubmed]

S. Sinha, E. van Nimwegen, and E. D. Siggia (2003). A Probabilistic Method to Detect Regulatory Modules. Bioinformatics, 2003, 19(S1). (Special issue on ISMB 2003.) (Best paper award, 2nd prize.) [Pubmed]

S. Sinha (2003). Discriminative Motifs. Journal of Computational Biology, 10(3), 599-615. [Pubmed] A preliminary version appeared in RECOMB, 2002.

S. Sinha, M. Tompa (2003) YMF, a Program for Discovery of Novel Transcription Factor Binding Sites by Statistical Overrepresentation, Nucleic Acids Research, Vol. 31, No. 13, pp. 3586-358. [Pubmed]

S. Sinha, M. Tompa (2003) Performance Comparison of Algorithms for Finding Transcription Factor Binding Sites, Third IEEE Symposium on Bioinformatics and Bioengineering, (BIBE), pp. 214-220.

S. Sinha and M. Tompa (2002). Discovery of Novel Transcription Factor Binding Sites by Statistical Overrepresentation. Nucleic Acids Research, 30(24), 5549-60. [Pubmed]

Y. Chen, R. Venkatesan, M. Cary, R. Pang, S. Sinha, M. Jakubowski. (2002) Oblivious hashing:  Silent Verification of Code Execution, Fifth International Workshop on Information Hiding (IHW).

M. Blanchette and S. Sinha (equal authors) (2001). Separating Real Motifs from their Artifacts. Bioinformatics, 17(S1). (Special issue on ISMB 2001.) [Pubmed]

R. Venkatesan, V. Vazirani, S. Sinha. (2001) A Graph-Theoretic Approach to Software Watermarking, Fourth International Workshop on Information Hiding,(IHW), pp. 157-168.

S. Sinha and M. Tompa (2000). A Statistical Method for Finding Transcription Factor Binding Sites. Proc. Eighth Intl. Conf. on Intelligent Systems for Molecular Biology (ISMB) 2000, 8:344-54. [Pubmed]