Showing papers by "Chris Sander published in 2006"

A novel class of small RNAs bind to MILI protein in mouse testes

Abstract: Small RNAs bound to Argonaute proteins recognize partially or fully complementary nucleic acid targets in diverse gene-silencing processes. A subgroup of the Argonaute proteins--known as the 'Piwi family'--is required for germ- and stem-cell development in invertebrates, and two Piwi members--MILI and MIWI--are essential for spermatogenesis in mouse. Here we describe a new class of small RNAs that bind to MILI in mouse male germ cells, where they accumulate at the onset of meiosis. The sequences of the over 1,000 identified unique molecules share a strong preference for a 5' uridine, but otherwise cannot be readily classified into sequence families. Genomic mapping of these small RNAs reveals a limited number of clusters, suggesting that these RNAs are processed from long primary transcripts. The small RNAs are 26-31 nucleotides (nt) in length--clearly distinct from the 21-23 nt of microRNAs (miRNAs) or short interfering RNAs (siRNAs)--and we refer to them as 'Piwi-interacting RNAs' or piRNAs. Orthologous human chromosomal regions also give rise to small RNAs with the characteristics of piRNAs, but the cloned sequences are distinct. The identification of this new class of small RNAs provides an important starting point to determine the molecular function of Piwi proteins in mammalian spermatogenesis.

Pathguide: a Pathway Resource List

Abstract: Pathguide: the Pathway Resource List (http://pathguide.org) is a meta-database that provides an overview of more than 190 web-accessible biological pathway and network databases. These include databases on metabolic pathways, signaling pathways, transcription factor targets, gene regulatory networks, genetic interactions, protein-compound interactions, and protein-protein interactions. The listed databases are maintained by diverse groups in different locations and the information in them is derived either from the scientific literature or from systematic experiments. Pathguide is useful as a starting point for biological pathway analysis and for content aggregation in integrated biological information systems.

Prediction of human microRNA targets.

Abstract: MicroRNAs (miRNAs) are small, nonprotein-coding RNAs that regulate gene expression Although hundreds of human miRNA genes have been discovered, the functions of most of these are unknown Computational predictions indicate that miRNAs, which account for at least 1% of human protein-coding genes, regulate protein production for thousands of or possibly all of human genes We discuss the functions of mammalian miRNAs and the experimental and computational methods used to detect and predict human miRNA target genes Anticipating their impact on genome-wide discovery of miRNA targets, we describe the various computational tools and web-based resources available to predict miRNA targets

cPath: open source software for collecting, storing, and querying biological pathways

Abstract: Biological pathways, including metabolic pathways, protein interaction networks, signal transduction pathways, and gene regulatory networks, are currently represented in over 220 diverse databases. These data are crucial for the study of specific biological processes, including human diseases. Standard exchange formats for pathway information, such as BioPAX, CellML, SBML and PSI-MI, enable convenient collection of this data for biological research, but mechanisms for common storage and communication are required. We have developed cPath, an open source database and web application for collecting, storing, and querying biological pathway data. cPath makes it easy to aggregate custom pathway data sets available in standard exchange formats from multiple databases, present pathway data to biologists via a customizable web interface, and export pathway data via a web service to third-party software, such as Cytoscape, for visualization and analysis. cPath is software only, and does not include new pathway information. Key features include: a built-in identifier mapping service for linking identical interactors and linking to external resources; built-in support for PSI-MI and BioPAX standard pathway exchange formats; a web service interface for searching and retrieving pathway data sets; and thorough documentation. The cPath software is freely available under the LGPL open source license for academic and commercial use. cPath is a robust, scalable, modular, professional-grade software platform for collecting, storing, and querying biological pathways. It can serve as the core data handling component in information systems for pathway visualization, analysis and modeling.

Detection of clonal rearrangement of T-cell receptor genes in the diagnosis of primary cutaneous CD30 lymphoproliferative disorders.

Abstract: BACKGROUND: Detection of clonality has been reported to be a helpful tool in the diagnosis of cutaneous lymphomas. Monoclonal rearrangement of T-cell receptor genes (TCR) was reported in fresh frozen tissue of lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (ALCL), but the diagnostic value of T-cell clonality in formalin-fixed, paraffin-embedded biopsies has so far not been assessed. METHODS: Detection of clonal rearrangement of TCRgamma genes by highly sensitive polymerase chain reaction-based automated high-resolution fragment analysis (AHRFA) in archival LyP (n = 18) and ALCL (n = 17) tissue. RESULTS: Detection of clonality differed significantly among the histologic forms of LyP as well as between LyP and ALCL with clonality found in none of the 10 biopsies of LyP type A and B, in 4/8 (50%) of the LyP type C specimens, and in 11/17 (65%) of ALCL cases. CONCLUSIONS: T-cell clonality can only be found in a minority (four of 18; 22%) of archival LyP specimens, even when employing a highly sensitive detection method and is thus of limited diagnostic value. Final diagnosis of LyP has to be based mainly on clinical, histologic, and immunohistochemical findings rather than on results of clonality studies.

BioPAX – biological pathway data exchange format

Abstract: Pathway information is vital for successful modeling of cellular systems. The over 215 on-line pathway databases vary widely in representation and coverage of biological processes, making their combined use extremely difficult. Future pathway information systems for querying, visualization, and analysis must support standard exchange formats to successfully integrate data on a large scale. BioPAX (www.biopax.org) is a data exchange format for biological pathways developed by pathway databases, such as BioCyc, WIT, Kyoto Encyclopedia of Genes and Genomes (KEGG), aMAZE, Integrating Network Objects with Hierarchies (INOH), PATIKA, Reactome, Biomolecular Interaction Database (BIND), and others. Level 1 supports metabolic pathways. Level 2 adds support for molecular interactions. Level 3 will add additional support for signal transduction and genetic regulatory networks. The ultimate goal of BioPAX is to enable seamless collection and use of pathway information so that it may be efficiently applied to answer biological questions. Keywords: pathway data integration; pathway database; standard exchange format; ontology; information system