Briefings in Bioinformatics

Identification of aberrant pathways and network activities from high-throughput data.

Publication Date: 2012 Jan 27 PMID: 22287794
Authors: Wang, J. - Zhang, Y. - Marian, C. - Ressom, H. W.
Journal: Brief Bioinform

Many complex diseases such as cancer are associated with changes in biological pathways and molecular networks rather than being caused by single gene alterations. A major challenge in the diagnosis and treatment of such diseases is to identify characteristic aberrancies in the biological pathways and molecular network activities and elucidate their relationship to the disease. This review presents recent progress in using high-throughput biological assays to decipher aberrant pathways and network activities. In particular, this review provides specific examples in which high-throughput data have been applied to identify relationships between diseases and aberrant pathways and network activities. The achievements in this field have been remarkable, but many challenges have yet to be addressed.

post to: CiteULike

BamView: visualizing and interpretation of next-generation sequencing read alignments.

Publication Date: 2012 Jan 24 PMID: 22253280
Authors: Carver, T. - Harris, S. R. - Otto, T. D. - Berriman, M. - Parkhill, J. - McQuillan, J. A.
Journal: Brief Bioinform

So-called next-generation sequencing (NGS) has provided the ability to sequence on a massive scale at low cost, enabling biologists to perform powerful experiments and gain insight into biological processes. BamView has been developed to visualize and analyse sequence reads from NGS platforms, which have been aligned to a reference sequence. It is a desktop application for browsing the aligned or mapped reads [Ruffalo, M, LaFramboise, T, Koyuturk, M. Comparative analysis of algorithms for next-generation sequencing read alignment. Bioinformatics 2011;27:2790-6] at different levels of magnification, from nucleotide level, where the base qualities can be seen, to genome or chromosome level where overall coverage is shown. To enable in-depth investigation of NGS data, various views are provided that can be configured to highlight interesting aspects of the data. Multiple read alignment files can be overlaid to compare results from different experiments, and filters can be applied to facilitate the interpretation of the aligned reads. As well as being a standalone application it can be used as an integrated part of the Artemis genome browser, BamView allows the user to study NGS data in the context of the sequence and annotation of the reference genome. Single nucleotide polymorphism (SNP) density and candidate SNP sites can be highlighted and investigated, and read-pair information can be used to discover large structural insertions and deletions. The application will also calculate simple analyses of the read mapping, including reporting the read counts and reads per kilobase per million mapped reads (RPKM) for genes selected by the user.Availability: BamView and Artemis are freely available software. These can be downloaded from their home pages:http://bamview.sourceforge.net/; http://www.sanger.ac.uk/resources/software/artemis/.Requirements: Java 1.6 or higher.

post to: CiteULike

Bioinformatics for personal genome interpretation.

Publication Date: 2012 Jan 13 PMID: 22247263
Authors: Capriotti, E. - Nehrt, N. L. - Kann, M. G. - Bromberg, Y.
Journal: Brief Bioinform

An international consortium released the first draft sequence of the human genome 10 years ago. Although the analysis of this data has suggested the genetic underpinnings of many diseases, we have not yet been able to fully quantify the relationship between genotype and phenotype. Thus, a major current effort of the scientific community focuses on evaluating individual predispositions to specific phenotypic traits given their genetic backgrounds. Many resources aim to identify and annotate the specific genes responsible for the observed phenotypes. Some of these use intra-species genetic variability as a means for better understanding this relationship. In addition, several online resources are now dedicated to collecting single nucleotide variants and other types of variants, and annotating their functional effects and associations with phenotypic traits. This information has enabled researchers to develop bioinformatics tools to analyze the rapidly increasing amount of newly extracted variation data and to predict the effect of uncharacterized variants. In this work, we review the most important developments in the field-the databases and bioinformatics tools that will be of utmost importance in our concerted effort to interpret the human variome.

post to: CiteULike

Multiscale modeling of macromolecular biosystems.

Publication Date: 2012 Jan 6 PMID: 22228511
Authors: Flores, S. C. - Bernauer, J. - Shin, S. - Zhou, R. - Huang, X.
Journal: Brief Bioinform

In this article, we review the recent progress in multiresolution modeling of structure and dynamics of protein, RNA and their complexes. Many approaches using both physics-based and knowledge-based potentials have been developed at multiple granularities to model both protein and RNA. Coarse graining can be achieved not only in the length, but also in the time domain using discrete time and discrete state kinetic network models. Models with different resolutions can be combined either in a sequential or parallel fashion. Similarly, the modeling of assemblies is also often achieved using multiple granularities. The progress shows that a multiresolution approach has considerable potential to continue extending the length and time scales of macromolecular modeling.

post to: CiteULike