Luke Alden Yancy, Jr. Mentor: Robert Riley Broad Institute of MIT & Harvard Cambridge, MA.
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Transcript of Luke Alden Yancy, Jr. Mentor: Robert Riley Broad Institute of MIT & Harvard Cambridge, MA.
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Luke Alden Yancy, Jr.Mentor: Robert Riley
Broad Institute of MIT & HarvardCambridge, MA
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Source: http://staff.vbi.vt.edu/pathport/pathinfo_images/Mycobacterium_tuberculosis/AerosolTransmission.jpg
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Source: WHO Stop TB Department, website: www.who.int/tb
Deaths Causes by TB (Estimated by WHO)
1998 1,751,858
2006 1,654,805
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Learn more about Mycobacterium Tuberculosis (Mtb) using analysis of gene expression data
Biclustering◦ Bimax (Prelic et al. 2006)◦ CC (Cheng and Church, 2000)◦ Plaid Model (Turner et al.
2003)◦ Spectral (Kluger et al. 2003)◦ Xmotifs (Murali and Kasif,
2003)
Traditional Clustering◦ K-Means (MacQueen, 1967)◦ Hierarchical (Eisen et al. 1998)
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Traditional Clustering
Biclustering
Gene Clusters Based on:
All Experiments Subsets of Experiments
Genes Assigned to Clusters:
One-to-OneMany-to-Many/ One-to-
Many
Reproducibility: YesNo (due to random steps in algorithm)
Source: Machine Learning and Its Applications to Biology, Tarca et al. 2007. (Editor: Fran Lewitter, Whitehead Institute)
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Bimax K-Means
Boshoff Data(Processed: 3924 Genes, 359
Experiments)
Clusters of Genes
Source: The Transcriptional Responses of Mycobacterium tuberculosis to Inhibitors of Metabolism. (Boshoff et al. 2004)
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(Source: http://www.nature.com/nature/journal/v409/n6823/full/4091007a0.html)
(proS loci of Mtb )
Cluster Operon
Gene Pair
(k)
(N)
(m) (n)
Significance of overlap k estimated using hypergeometric distribution:
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Bimax Biclustering Operon Overlap
Source: Prolinks: a database of protein functional linkages derived from coevolution (Bowers et al. 2005)
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Random step – lacks reproducibility
No biological soundness
Artificial arrangement of data
◦ Large data sets produce statistically significant, but small clusters
Practicality
◦ Implementation
◦ Large Input Data Sets
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K-Means clustering performs better than biclustering on our data set
Next, use motif recognition methods to identify regulatory motifs in clusters
Further development of improved biclustering algorithms
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Project TeamRobert Riley (Mentor)Brian Weiner
The Broad InstitueEric LanderCore MembersSRPG Program Members
Summer Research Program in Genomics (SRPG)Shawna YoungBruce BirrenLucia VielmaMaura Silverstein