Computational comparative genomics : genes, regulation, evolution

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (p. 95-99).Understanding the biological signals encoded in a genome is a key challenge of computational biology. These signals are encoded in the four-nucleotide alphabet of DNA and are responsible for all molecular processes in the cell. In particular, the genome contains the blueprint of all protein-coding genes and the regulatory motifs used to coordinate the expression of these genes. Comparative genome analysis of related species provides a general approach for identifying these functional elements, by virtue of their stronger conservation across evolutionary time. In this thesis we address key issues in the comparative analysis of multiple species. We present novel computational methods in four areas (1) the automatic comparative annotation of multiple species and the determination of orthologous genes and intergenic regions (2) the validation of computationally predicted protein-coding genes (3) the systematic de-novo identification of regulatory motifs (4) the determination of combinatorial interactions between regulatory motifs. We applied these methods to the comparative analysis of four yeast genomes, including the best-studied eukaryote, Saccharomyces cerevisiae or baker's yeast. Our results show that nearly a tenth of currently annotated yeast genes are not real, and have refined the structure of hundreds of genes. Additionally, we have automatically discovered a dictionary of regulatory motifs without any previous biological knowledge. These include most previously known regulatory motifs, and a number of novel motifs. We have automatically assigned candidate functions to the majority of motifs discovered, and defined biologically meaningful combinatorial interactions between them. Finally, we defined the regions and mechanisms of rapid evolution, with important biological implications.(cont.) Our results demonstrate the central role of computational tools in modem biology. The analyses presented in this thesis have revealed biological findings that could not have been discovered by traditional genetic methods, regardless of the time or effort spent. The methods presented are general and may present a new paradigm for understanding the genome of any single species. They are currently being applied to a kingdom-wide exploration of fungal genomes, and the comparative analysis of the human genome with that of the mouse and other mammals.by Manolis (Kellis) Kamvysselis.Ph.D

Cognitive abstraction approach to sketch-based image retrieval

Thesis (S.B. and M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 1999.Includes bibliographical references (leaves 151-157).This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.As digital media become more popular, corporations and individuals gather an increasingly large number of digital images. As a collection grows to more than a few hundred images, the need for search becomes crucial. This thesis is addressing the problem of retrieving from a small database a particular image previously seen by the user. This thesis combines current findings in cognitive science with the knowledge of previous image retrieval systems to present a novel approach to content based image retrieval and indexing. We focus on algorithms which abstract away information from images in the same terms that a viewer abstracts information from an image. The focus in Imagina is on the matching of regions, instead of the matching of global measures. Multiple representations, focusing on shape and color, are used for every region. The matches of individual regions are combined using a saliency metric that accounts for differences in the distributions of metrics. Region matching along with configuration determines the overall match between a query and an image.by Manolis Kamvysselis and Ovidiu Marina.S.B.and M.Eng

A New Voronoi-Based Surface Reconstruction Algorithm

We describe our experience with a new algorithm for the reconstruction of surfaces from unorganized sample points in IR3. The algorthim is the first for this problem with provable guarantees. Given a ''good sample'' from a smooth surface, the output is guaranteed to be topologically correct and convergent to the original surface as the sampling sensity increases. The definition of a good sample is itself interesting: the required sampling density varies locally, rigorously capturing the intuitive notion that featureless areas can be reconstructed from fewer samples. The output mesh interpolates, rather than approximates, the input points. Our algorithm is based on the three-dimensional Voronoi diagram. Given a good program for thsi fundamental subroutine, the algorithm is quite easy to implement

A New Voronoi-Based Surface Reconstruction Algorithm

We describe our experience with a new algorithm for the reconstruction of surfaces from unorganized sample points in IR 3 . The algorithm is the first for this problem with provable guarantees. Given a "good sample" from a smooth surface, the output is guaranteed to be topologically correct and convergent to the original surface as the sampling density increases. The definition of a good sample is itself interesting: the required sampling density varies locally, rigorously capturing the intuitive notion that featureless areas can be reconstructed from fewer samples. The output mesh interpolates, rather than approximates, the input points. Our algorithm is based on the three-dimensional Voronoi diagram. Given a good program for this fundamental subroutine, the algorithm is quite easy to implement. Keywords: Medial axis, Sampling, Delaunay triangulation, Computational Geometry 1 Introduction The process of turning a set of sample points in IR 3 into a computer graphics model genera..

The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysis of RNA sequencing data from 1641 samples across 43 tissues from 175 individuals, generated as part of the pilot phase of the Genotype-Tissue Expression (GTEx) project. We describe the landscape of gene expression across tissues, catalog thousands of tissue-specific and shared regulatory expression quantitative trait loci (eQTL) variants, describe complex network relationships, and identify signals from genome-wide association studies explained by eQTLs. These findings provide a systematic understanding of the cellular and biological consequences of human genetic variation and of the heterogeneity of such effects among a diverse set of human tissues

Whole-genome comparative annotation and regulatory motif discovery in multiple yeast species; 2003

In [13] we reported the genome sequences of S. paradoxus, S. mikatae and S. bayanus and compared these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed the identification of functionally important sequences, both coding and non-coding. In this companion paper we describe the mathematical and algorithmic results underpinning the analysis of these genomes. We developed methods for the automatic comparative annotation of the four species and the determination of orthologous genes and intergenic regions. The algorithms enabled the automatic identification of orthologs for more than 90 % of genes despite the large number of duplicated genes in the yeast genome, and the discovery of recent gene family expansions and genome rearrangements. We also developed a test to validat