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 PLoS Genetics
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 Database
The Cancer Genomics Hub (CGHub) is the online repository of the sequencing programs of the National Cancer Institute (NCI), including The Cancer Genomics Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE) and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) projects, with data from 25 different types of cancer. ...
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 Molecular Biology and Evolution
Nucleotide substitution in both coding and noncoding regions is context-dependent, in the sense that substitution rates depend on the identity of neighboring bases. Context-dependent substitution has been modeled in the case of two sequences and an unrooted phylogenetic tree, but it has only been accommodated in limited ways with more general phylo...
Published in Nucleic Acids Research
The UCSC Cancer Genomics Browser (https://genome-cancer.ucsc.edu/) is a set of web-based tools to display, investigate and analyse cancer genomics data and its associated clinical information. The browser provides whole-genome to base-pair level views of several different types of genomics data, including some next-generation sequencing platforms. ...
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 Genome Research
It is believed that most modern mammalian lineages arose from a series of rapid speciation events near the Cretaceous-Tertiary boundary. It is shown that such a phylogeny makes the common ancestral genome sequence an ideal target for reconstruction. Simulations suggest that with methods currently available, we can expect to get 98% of the bases cor...
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 ...
Enhancers and antisense RNAs play key roles in transcriptional regulation through differing mechanisms. Recent studies have demonstrated that enhancers are often associated with non-coding RNAs (ncRNAs), yet the functional role of these enhancer:ncRNA associations is unclear. Using RNA-Sequencing to interrogate the transcriptomes of undifferentiate...
Published in Proceedings of the National Academy of Sciences
At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Recent work has highlighted a han...
Published in Bioinformatics
Published in Journal of Computational Biology
We introduce a data structure, analysis, and visualization scheme called a cactus graph for comparing sets of related genomes. In common with multi-break point graphs and A-Bruijn graphs, cactus graphs can represent duplications and general genomic rearrangements, but additionally, they naturally decompose the common substructures in a set of relat...
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 GigaScience
Everyone loves the birds of the world. From their haunting songs and majesty of flight to dazzling plumage and mating rituals, bird watchers - both amateurs and professionals - have marveled for centuries at their considerable adaptations. Now, we are offered a special treat with the publication of a series of papers in dedicated issues of Science,...
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 Nature Methods
Published in Proceedings of the National Academy of Sciences
At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Recent work has highlighted a han...
