Published in Journal of Computational Biology
We introduce a new system, called shortHMM, for predicting exons, which predicts individual exons using two related genomes. In this system, we build a hidden semi-Markov model to identify exons. In the hidden Markov model, we propose joint probability models of nucleotides in introns, splice sites, 5 UTR, 3 UTR, and intergenic regions by exploitin...
Published in Science
The gain, loss, and modification of gene regulatory elements may underlie a substantial proportion of phenotypic changes on animal lineages. To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans. These putative regulatory r...
Published in Nature Methods
Published in Nucleic Acids Research
Launched in 2001 to showcase the draft human genome assembly, the UCSC Genome Browser database (http://genome.ucsc.edu) and associated tools continue to grow, providing a comprehensive resource of genome assemblies and annotations to scientists and students worldwide. Highlights of the past year include the release of a browser for the first new hu...
Published in Science
Ultraconserved elements in the human genome are defined as stretches of at least 200 base pairs of DNA that match identically with corresponding regions in the mouse and rat genomes. Most ultraconserved elements are noncoding and have been evolutionarily conserved since mammal and bird ancestors diverged over 300 million years ago. The reason for t...
Published in Nucleic Acids Research
The University of California, Santa Cruz Genome Browser Database contains, as of September 2006, sequence and annotation data for the genomes of 13 vertebrate and 19 invertebrate species. The Genome Browser displays a wide variety of annotations at all scales from the single nucleotide level up to a full chromosome and includes assembly data, genes...
Published in Nature Methods
Classical approaches to determine structures of noncoding RNA (ncRNA) probed only one RNA at a time with enzymes and chemicals, using gel electrophoresis to identify reactive positions. To accelerate RNA structure inference, we developed fragmentation sequencing (FragSeq), a high-throughput RNA structure probing method that uses high-throughput RNA...
Published in Journal of the American Medical Informatics Association
The world s genomics data will never be stored in a single repository - rather, it will be distributed among many sites in many countries. No one site will have enough data to explain genotype to phenotype relationships in rare diseases; therefore, sites must share data. To accomplish this, the genetics community must forge common standards and pro...
Published in Proceedings of the National Academy of Sciences
We use an integrated approach to understand breast cancer heterogeneity by modeling mRNA, copy number alterations, microRNAs, and methylation in a pathway context utilizing the pathway recognition algorithm using data integration on genomic models (PARADIGM). We demonstrate that combining mRNA expression and DNA copy number classified the patients ...
Published in Genome Biology and Evolution
Fast evolving regions of many metazoan genomes show a bias toward substitutions that change weak (A,T) into strong (G,C) base pairs. Single-nucleotide polymorphisms (SNPs) do not share this pattern, suggesting that it results from biased fixation rather than biased mutation. Supporting this hypothesis, analyses of polymorphism in specific regions o...
Published in Journal of Computational Biology
A new method for detecting remote protein homologies is introduced and shown to perform well in classifying protein domains by SCOP superfamily. The method is a variant of support vector machines using a new kernel function. The kernel function is derived from a generative statistical model for a protein family, in this case a hidden Markov model. ...
Published in Bioinformatics
Published in Genome Research
The National Institutes of Health s Mammalian Gene Collection (MGC) project was designed to generate and sequence a publicly accessible cDNA resource containing a complete open reading frame (ORF) for every human and mouse gene. The project initially used a random strategy to select clones from a large number of cDNA libraries from diverse tissues....
Published in Proceedings of the National Academy of Sciences
The evolutionary forces that establish and hone target gene networks of transcription factors are largely unknown. Transposition of retroelements may play a role, but its global importance, beyond a few well described examples for isolated genes, is not clear. We report that LTR class I endogenous retrovirus (ERV) retroelements impact considerably ...
Published in Genome Research
Comparative sequence analysis has become an essential component of studies aiming to elucidate genome function. The increasing availability of genomic sequences from multiple vertebrates is creating the need for computational methods that can detect highly conserved regions in a robust fashion. Towards that end, we are developing approaches for ide...
Published in Genome Research
Much attention has been given to the problem of creating reliable multiple sequence alignments in a model incorporating substitutions, insertions, and deletions. Far less attention has been paid to the problem of optimizing alignments in the presence of more general rearrangement and copy number variation. Using Cactus graphs, recently introduced f...
Published in Systematic Biology
Published in Nature Methods
Published in Biochemistry
Published in Proceedings of the National Academy of Sciences
Squamous cell carcinomas (SCCs) are one of the most frequent forms of human malignancy, but, other than TP53 mutations, few causative somatic aberrations have been identified. We identified NOTCH1 or NOTCH2 mutations in ~75% of cutaneous SCCs and in a lesser fraction of lung SCCs, defining a spectrum for the most prevalent tumor suppressor specific...
