Showing papers by "Aron Marchler-Bauer published in 2010"

The NCBI BioSystems database

Abstract: The NCBI BioSystems database, found at http://www.ncbi.nlm.nih.gov/biosystems/, centralizes and cross-links existing biological systems databases, increasing their utility and target audience by integrating their pathways and systems into NCBI resources. This integration allows users of NCBI's Entrez databases to quickly categorize proteins, genes and small molecules by metabolic pathway, disease state or other BioSystem type, without requiring time-consuming inference of biological relationships from the literature or multiple experimental datasets.

Inferred Biomolecular Interaction Server--a web server to analyze and predict protein interacting partners and binding sites.

Abstract: IBIS is the NCBI Inferred Biomolecular Interaction Server. This server organizes, analyzes and predicts interaction partners and locations of binding sites in proteins. IBIS provides annotations for different types of binding partners (protein, chemical, nucleic acid and peptides), and facilitates the mapping of a comprehensive biomolecular interaction network for a given protein query. IBIS reports interactions observed in experimentally determined structural complexes of a given protein, and at the same time IBIS infers binding sites/interacting partners by inspecting protein complexes formed by homologous proteins. Similar binding sites are clustered together based on their sequence and structure conservation. To emphasize biologically relevant binding sites, several algorithms are used for verification in terms of evolutionary conservation, biological importance of binding partners, size and stability of interfaces, as well as evidence from the published literature. IBIS is updated regularly and is freely accessible via http://www.ncbi.nlm.nih.gov/Structure/ibis/ibis.html.

AlexSys: a knowledge-based expert system for multiple sequence alignment construction and analysis

Abstract: Multiple sequence alignment (MSA) is a cornerstone of modern molecular biology and represents a unique means of investigating the patterns of conservation and diversity in complex biological systems. Many different algorithms have been developed to construct MSAs, but previous studies have shown that no single aligner consistently outperforms the rest. This has led to the development of a number of ‘meta-methods’ that systematically run several aligners and merge the output into one single solution. Although these methods generally produce more accurate alignments, they are inefficient because all the aligners need to be run first and the choice of the best solution is made a posteriori. Here, we describe the development of a new expert system, AlexSys, for the multiple alignment of protein sequences. AlexSys incorporates an intelligent inference engine to automatically select an appropriate aligner a priori, depending only on the nature of the input sequences. The inference engine was trained on a large set of reference multiple alignments, using a novel machine learning approach. Applying AlexSys to a test set of 178 alignments, we show that the expert system represents a good compromise between alignment quality and running time, making it suitable for high throughput projects. AlexSys is freely available from http://alnitak.u-strasbg.fr/~aniba/alexsys.

Abstract 95: Phylogenetic classification, structural evolution, and functional divergence of the ABC-type transporters: Inferences derived from CDTree/Cn3D software applications

Abstract: The NCBI9s Conserved Domain Database (CDD; http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml), is a collection of annotated multiple sequence alignment models representing ancient conserved protein domains, basic units of protein function and protein evolution. Domain models are annotated with functional sites and can be viewed as sequence alignments together with corresponding 3D structure using the CDTree/Cn3D software applications. CDTree/Cn3D is a domain hierarchy editor which lets the user view and examine conserved domain hierarchies interactively and in great detail. A domain hierarchy is a structured collection of domain models reflecting the domain family9s molecular evolution. Here we present our current, functionally annotated evolutionary classifications of the nucleotide-binding domain, transmembrane domain, and periplasmic binding proteins of the ABC (ATP binding cassette)-type transport systems which are involved in the transport of a wide variety of substrates such as sugars, ions, peptides, and more complex organic molecules across membranes. Mutations in ABC transporters cause or contribute to multi-drug resistance, cystic fibrosis, and a range of other human diseases. Using CDTree/Cn3D functionality, subfamilies present in diverse organisms were inferred from the multiple sequence alignments, phylogenetic trees, and the domain architectures of the proteins involved. Furthermore subfamilies, some of which are only comprised of uncharacterized proteins, were annotated with molecular and cellular function and the location of conserved sites, as available in the literature and evident from protein 3D structure. We demonstrate the utility of CDTree/Cn3D in studying the molecular evolution of protein and domain families, and in accelerating the discovery of orthologous groups. CDTree/Cn3D are freely available for download via the CDD website. A version of CDTree, which supports both Mac OSX and Windows operating systems, has recently been made available. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 95.