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MicroRNAs (miRNAs) have recently been discovered as an important class of non-coding RNA genes that play a major role in regulating gene expression, providing a means to control the relative amounts of mRNA transcripts and their protein products. Although much work has been done in the genome-wide computational prediction of miRNA genes and their target mRNAs, two open questions are how miRNAs regulate...
We have combined four different types of functional genomic data to create high coverage protein interaction networks for 11 microbes. Our integration algorithm naturally handles statistically dependent predictors and automatically corrects for differing noise levels and data corruption in different evidence sources. We find that many of the predictions in each integrated network hinge on moderate...
Relationships among amino acids determine stability and function and are also constrained by evolutionary history. We develop a probabilistic hypergraph model of residue relationships that generalizes traditional pairwise contact potentials to account for the statistics of multi-residue interactions. Using this model, we detected non-random associations in protein families and in the protein database...
We describe a new approach for comparing cellular-biological networks, and finding conserved regions in two or more such networks. We use the length of describing one network, given the description of the other one, as a distance measure. We employ these distances as inputs for generating phylogenetic trees. Our algorithms are fast enough for generating phylogenetic tree of more than two hundreds...
Computational and comparative analysis of protein-protein interaction (PPI) networks enable understanding of the modular organization of the cell through identification of functional modules and protein complexes. These analysis techniques generally rely on topological features such as connectedness, based on the premise that functionally related proteins are likely to interact densely and that these...
The unsupervised clustering analysis of data from temporal or dose-response experiments is one of the most important and challenging tasks of microarray data anlysis. Here we present an extension of CAGED (Cluster Analysis of Gene Expression Dynamics, one of the most commonly used programs) to identify similar gene expression patterns measured in either short time-course or dose-response microarray...
Pharmacogenomics and clinical studies that measure the temporal expression levels of patients can identify important pathways and biomarkers that are activated during disease progression or in response to treatment. However, researchers face a number of challenges when trying to combine expression profiles from these patients. Unlike studies that rely on lab animals or cell lines, individuals vary...
Recent developments in the omics field have provided the community with comprehensive repertoires of RNAs, proteins, metabolites that constitute the cell building blocks. The next challenge resides in the understanding of how the “pieces” of this huge puzzle assemble, combine and contribute to the assembly of a coherent entity: a cell. Biology relies on the concerted action of a number of molecular...
Genomic distances based on the number of rearrangement steps – inversions, transpositions, reciprocal translocations – necessary to convert the gene or segment order of one genome to that of another are potentially meaningful measures of evolutionary divergence. The significance of a comparison between two genomes, however, depends on how it differs from the case where the order of the n segments...
We propose an improved statistic for detecting over-represented Gene Ontology (GO) annotations in gene sets. While the current methods treats each term independently and hence ignores the structure of the GO hierarchy, our approach takes parent-child relationships into account. Over-representation of a term is measured with respect to the presence of its parental terms in the set. This resolves the...
Reliable automatic protein function annotation requires methods for detecting orthologs with known function from closely related species. While current approaches are restricted to finding ortholog clusters from complete proteomes, most annotation problems arise in the context of partially sequenced genomes. We use a combinatorial optimization method for extracting candidate ortholog clusters robustly...
MicroRNAs (miRNAs) have recently been discovered as an important class of non-coding RNA genes that play a major role in regulating gene expression, providing a means to control the relative amounts of mRNA transcripts and their protein products. Although much work has been done in the genome-wide computational prediction of miRNA genes and their target mRNAs, two open questions are how miRNAs regulate...
There is a resurgence of interest in RNA secondary structure prediction problem (a.k.a. the RNA folding problem) due to the discovery of many new families of non-coding RNAs with a variety of functions. The vast majority of the computational tools for RNA secondary structure prediction are based on free energy minimization. Here the goal is to compute a non-conflicting collection of structural elements...
In this paper, we address the problem of discovering novel non-coding RNA (ncRNA) using primary sequence, and secondary structure conservation, focusing on ncRNA families with pseudo-knotted structures. Our main technical result is an efficient algorithm for computing an optimum structural alignment of an RNA sequence against a genomic substring. This algorithm finds two applications. First, by scanning...
In each the 10 years Recomb has existed as an annual conference, there has been an Ulam Lecture, beginning with the 1997 Ulam Lecture delivered in Santa Fe by Eric Lander. While intended by the conference organizers to be a less technical and more casual lecture, it is difficult for a scientist not to speak about their own science and understandably that is just what has happened. In this year’s Ulam...
In this paper, we present CONTRAlign, an extensible and fully automatic framework for parameter learning and protein pairwise sequence alignment using pair conditional random fields. When learning a substitution matrix and gap penalties from as few as 20 example alignments, CONTRAlign achieves alignment accuracies competitive with available modern tools. As confirmed by rigorous cross-validated testing,...
We present a new approach to managing redundancy in sequence databanks such as GenBank. We store clusters of near-identical sequences as a representative union-sequence and a set of corresponding edits to that sequence. During search, the query is compared to only the union-sequences representing each cluster; cluster members are then only reconstructed and aligned if the union-sequence achieves a...
So far, most methods for identifying sequences under selection based on comparative sequence data have either assumed selectional pressures are the same across all branches of a phylogeny, or have focused on changes in specific lineages of interest. Here, we introduce a more general method that detects sequences that have either come under selection, or begun to drift, on any lineage. The method is...
We introduce a Markov model for the evolution of a gene family along a phylogeny. The model includes parameters for the rates of horizontal gene transfer, gene duplication, and gene loss, in addition to branch lengths in the phylogeny. The likelihood for the changes in the size of a gene family across different organisms can be calculated in O(N+hM2) time and O(N+M2) space, where ...
The Robinson-Foulds (RF) metric is the measure most widely used in comparing phylogenetic trees; it can be computed in linear time using Day’s algorithm. When faced with the need to compare large numbers of large trees, however, even linear time becomes prohibitive. We present a randomized approximation scheme that provides, with high probability, a (1+ε) approximation of the true RF metric for all...
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