RNA-Seq mapping and detection of gene fusions with a suffix array algorithm.

High-throughput RNA sequencing enables quantification of transcripts (both known and novel), exon/exon junctions and fusions of exons from different genes. Discovery of gene fusions-particularly those expressed with low abundance- is a challenge with short- and medium-length sequencing reads. To address this challenge, we implemented an RNA-Seq mapping pipeline within the LifeScope software.

Tumor transcriptome sequencing reveals allelic expression imbalances associated with copy number alterations.

Due to growing throughput and shrinking cost, massively parallel sequencing is rapidly becoming an attractive alternative to microarrays for the genome-wide study of gene expression and copy number alterations in primary tumors. The sequencing of transcripts (RNA-Seq) should offer several advantages over microarray-based methods, including the ability to detect somatic mutations and accurately measure allele-specific expression. To investigate these advantages we have applied a novel, strand-specific RNA-Seq method to tumors and matched normal tissue from three patients with oral squamous cell carcinomas.

Perturbation of interaction networks for application to cancer therapy.

We present a computational approach for studying the effect of potential drug combinations on the protein networks associated with tumor cells. The majority of therapeutics are designed to target single proteins, yet most diseased states are characterized by a combination of many interacting genes and proteins. Using the topology of protein-protein interaction networks, our methods can explicitly model the possible synergistic effect of targeting multiple proteins using drug combinations in different cancer types.

The complete genome of Rhodococcus sp. RHA1 provides insights into a catabolic powerhouse.

Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids.

Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach.

Background: High throughput sequencing-by-synthesis is an emerging technology that allows the rapid production of millions of bases of data. Although the sequence reads are short, they can readily be used for re-sequencing. By re-sequencing the mRNA products of a cell, one may rapidly discover polymorphisms and splice variants particular to that cell.

Sequence biases in large scale gene expression profiling data.

We present the results of a simple, statistical assay that measures the G+C content sensitivity bias of gene expression experiments without the requirement of a duplicate experiment. We analyse five gene expression profiling methods: Affymetrix GeneChip, Long Serial Analysis of Gene Expression (LongSAGE), LongSAGELite, 'Classic' Massively Parallel Signature Sequencing (MPSS) and 'Signature' MPSS. We demonstrate the methods have systematic and random errors leading to a different G+C content sensitivity.

Physical map-assisted whole-genome shotgun sequence assemblies.

We describe a targeted approach to improve the contiguity of whole-genome shotgun sequence (WGS) assemblies at run-time, using information from Bacterial Artificial Chromosome (BAC)-based physical maps. Clone sizes and overlaps derived from clone fingerprints are used for the calculation of length constraints between any two BAC neighbors sharing 40% of their size. These constraints are used to promote the linkage and guide the arrangement of sequence contigs within a sequence scaffold at the layout phase of WGS assemblies.

Sequencing and analysis of 10,967 full-length cDNA clones from Xenopus laevis and Xenopus tropicalis reveals post-tetraploidization transcriptome remodeling.

Sequencing of full-insert clones from full-length cDNA libraries from both Xenopus laevis and Xenopus tropicalis has been ongoing as part of the Xenopus Gene Collection Initiative. Here we present 10,967 full ORF verified cDNA clones (8049 from X. laevis and 2918 from X.

A mouse atlas of gene expression: large-scale digital gene-expression profiles from precisely defined developing C57BL/6J mouse tissues and cells.

We analyzed 8.55 million LongSAGE tags generated from 72 libraries. Each LongSAGE library was prepared from a different mouse tissue.

Assessment and integration of publicly available SAGE, cDNA microarray, and oligonucleotide microarray expression data for global coexpression analyses.

Large amounts of gene expression data from several different technologies are becoming available to the scientific community. A common practice is to use these data to calculate global gene coexpression for validation or integration of other "omic" data. To assess the utility of publicly available datasets for this purpose we have analyzed Homo sapiens data from 1202 cDNA microarray experiments, 242 SAGE libraries, and 667 Affymetrix oligonucleotide microarray experiments.

Management and visualization of whole genome shotgun assemblies using SAM.

We have designed and implemented a system to manage whole genome shotgun sequences and whole genome sequence assembly data flow. The Sequence Assembly Manager (SAM) consists primarily of a MySQL relational database and Perl applications designed to easily manipulate and coordinate the analysis of sequence information and to view and report genome assembly progress through its Common Gateway Interface (CGI) web interface. The application includes a tool to compare sequence assemblies to fingerprint maps that has been used successfully to improve and validate both maps and sequence assemblies of the Rhodococcus sp.

Sockeye: a 3D environment for comparative genomics.

Comparative genomics techniques are used in bioinformatics analyses to identify the structural and functional properties of DNA sequences. As the amount of available sequence data steadily increases, the ability to perform large-scale comparative analyses has become increasingly relevant. In addition, the growing complexity of genomic feature annotation means that new approaches to genomic visualization need to be explored.