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Results for “proteome mapping”

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At least 649 records · Page 36Linked to original sources
PubMed2006

Protein bipartivity and essentiality in the yeast protein-protein interaction network.

Protein-protein interaction networks (PINs) are structured by means of a few highly connected proteins linked to a large number of less-connected ones. Essential proteins have been found to be more abundant among these highly connected proteins. Here we demonstrate that the likelihood that removal of a protein in a PIN will prove lethal to yeast correlates with the lack of bipartivity of the protein. A protein is bipartite if it can be partitioned in such a way that there are two groups of proteins with intergroup, but not intragroup, interactions. The abundance of essential proteins found among the least bipartite proteins clearly exceeds that found among the most connected ones. For instance, among the top 50 proteins ranked by their lack of bipartivity 62% are essential proteins. However, this percentage is only 38% for proteins ranked according to their number of interactions. Protein bipartivity also surpasses another 5 measures of protein centrality in yeast PIN in identifying essential proteins and doubles the number of essential proteins selected at random. We propose a possible mechanism for the evolution of essential proteins in yeast PIN based on the duplication-divergence scheme. We conclude that a replica protein evolving from a nonbipartite target will also be nonbipartite with high probability. Consequently, these new replicas evolving from nonbipartite (essential) targets will with high probability be essential.

Evolution, Molecular↗
PubMed2002

New names for old disciplines.

Since the completion of the human genome map, genomics, proteomics and pharmacogenomics have become popular headings. In this review some 40 years of development in research and laboratory diagnosis of inborn errors of metabolism are summarized. It is shown that collaborative approaches of clinicians, geneticists, pathologists, biochemists and molecular biologists have contributed significantly to the (prenatal) diagnosis, genetic counselling and prevention of simple gene disorders, and in some instances to successful treatment. DNA technology widens the range to predictive risk testing for multifactorial disorders manifesting in adulthood. This offers new perspectives for potential patients and their close relatives, but also poses new psychosocial and ethical problems. Despite high expectations of new technologies in the development of new medicines for multifactorial disorders, examples of previous studies on the molecular etiology and pathogenesis of monogenic diseases indicate that a long way is ahead of us. Also the treatment of rare disorders and equal access to cure and care in the Third World need great attention.

DNA↗
PubMedDate not supplied

The DNA sequence and comparative analysis of human chromosome 20.

The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.

Animals↗
PubMed2002

Initial sequencing and comparative analysis of the mouse genome.

The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.

Animals↗
PubMed2004

Genome duplication in the teleost fish Tetraodon nigroviridis reveals the early vertebrate proto-karyotype.

Tetraodon nigroviridis is a freshwater puffer fish with the smallest known vertebrate genome. Here, we report a draft genome sequence with long-range linkage and substantial anchoring to the 21 Tetraodon chromosomes. Genome analysis provides a greatly improved fish gene catalogue, including identifying key genes previously thought to be absent in fish. Comparison with other vertebrates and a urochordate indicates that fish proteins have diverged markedly faster than their mammalian homologues. Comparison with the human genome suggests approximately 900 previously unannotated human genes. Analysis of the Tetraodon and human genomes shows that whole-genome duplication occurred in the teleost fish lineage, subsequent to its divergence from mammals. The analysis also makes it possible to infer the basic structure of the ancestral bony vertebrate genome, which was composed of 12 chromosomes, and to reconstruct much of the evolutionary history of ancient and recent chromosome rearrangements leading to the modern human karyotype.

Animals↗
PubMed2006

Insights into social insects from the genome of the honeybee Apis mellifera.

Here we report the genome sequence of the honeybee Apis mellifera, a key model for social behaviour and essential to global ecology through pollination. Compared with other sequenced insect genomes, the A. mellifera genome has high A+T and CpG contents, lacks major transposon families, evolves more slowly, and is more similar to vertebrates for circadian rhythm, RNA interference and DNA methylation genes, among others. Furthermore, A. mellifera has fewer genes for innate immunity, detoxification enzymes, cuticle-forming proteins and gustatory receptors, more genes for odorant receptors, and novel genes for nectar and pollen utilization, consistent with its ecology and social organization. Compared to Drosophila, genes in early developmental pathways differ in Apis, whereas similarities exist for functions that differ markedly, such as sex determination, brain function and behaviour. Population genetics suggests a novel African origin for the species A. mellifera and insights into whether Africanized bees spread throughout the New World via hybridization or displacement.

Animals↗
PubMed2002

Analyzing yeast protein-protein interaction data obtained from different sources.

High-throughput methods for detecting protein interactions, such as mass spectrometry and yeast two-hybrid assays, continue to produce vast amounts of data that may be exploited to infer protein function and regulation. As this article went to press, the pool of all published interaction information on Saccharomyces cerevisiae was 15,143 interactions among 4,825 proteins, and power-law scaling supports an estimate of 20,000 specific protein interactions. To investigate the biases, overlaps, and complementarities among these data, we have carried out an analysis of two high-throughput mass spectrometry (HMS)-based protein interaction data sets from budding yeast, comparing them to each other and to other interaction data sets. Our analysis reveals 198 interactions among 222 proteins common to both data sets, many of which reflect large multiprotein complexes. It also indicates that a "spoke" model that directly pairs bait proteins with associated proteins is roughly threefold more accurate than a "matrix" model that connects all proteins. In addition, we identify a large, previously unsuspected nucleolar complex of 148 proteins, including 39 proteins of unknown function. Our results indicate that existing large-scale protein interaction data sets are nonsaturating and that integrating many different experimental data sets yields a clearer biological view than any single method alone.

Chromatography, Liquid↗
PubMed2005

Detection of parallel functional modules by comparative analysis of genome sequences.

Parallel functional modules are separate sets of proteins in an organism that catalyze the same or similar biochemical reactions but act on different substrates or use different cofactors. They originate by gene duplication during evolution. Parallel functional modules provide versatility and complexity to organisms, and increase cellular flexibility and robustness. We have developed a four-step approach for genome-wide discovery of parallel modules from protein functional linkages. From ten genomes, we identified 37 cellular systems that consist of parallel functional modules. This approach recovers known parallel complexes and pathways, and discovers new ones that conventional homology-based methods did not previously reveal, as illustrated by examples of peptide transporters in Escherichia coli and nitrogenases in Rhodopseudomonas palustris. The approach untangles intertwined functional linkages between parallel functional modules and expands our ability to decode protein functions from genome sequences.

Amino Acid Sequence↗
PubMed2005

Probabilistic model of the human protein-protein interaction network.

A catalog of all human protein-protein interactions would provide scientists with a framework to study protein deregulation in complex diseases such as cancer. Here we demonstrate that a probabilistic analysis integrating model organism interactome data, protein domain data, genome-wide gene expression data and functional annotation data predicts nearly 40,000 protein-protein interactions in humans-a result comparable to those obtained with experimental and computational approaches in model organisms. We validated the accuracy of the predictive model on an independent test set of known interactions and also experimentally confirmed two predicted interactions relevant to human cancer, implicating uncharacterized proteins into definitive pathways. We also applied the human interactome network to cancer genomics data and identified several interaction subnetworks activated in cancer. This integrative analysis provides a comprehensive framework for exploring the human protein interaction network.

Chromosome Mapping↗
PubMed2006

Modeling cellular machinery through biological network comparison.

Molecular networks represent the backbone of molecular activity within the cell. Recent studies have taken a comparative approach toward interpreting these networks, contrasting networks of different species and molecular types, and under varying conditions. In this review, we survey the field of comparative biological network analysis and describe its applications to elucidate cellular machinery and to predict protein function and interaction. We highlight the open problems in the field as well as propose some initial mathematical formulations for addressing them. Many of the methodological and conceptual advances that were important for sequence comparison will likely also be important at the network level, including improved search algorithms, techniques for multiple alignment, evolutionary models for similarity scoring and better integration with public databases.

Algorithms↗
PubMed2005

Reverse engineering of regulatory networks in human B cells.

Cellular phenotypes are determined by the differential activity of networks linking coregulated genes. Available methods for the reverse engineering of such networks from genome-wide expression profiles have been successful only in the analysis of lower eukaryotes with simple genomes. Using a new method called ARACNe (algorithm for the reconstruction of accurate cellular networks), we report the reconstruction of regulatory networks from expression profiles of human B cells. The results are suggestive a hierarchical, scale-free network, where a few highly interconnected genes (hubs) account for most of the interactions. Validation of the network against available data led to the identification of MYC as a major hub, which controls a network comprising known target genes as well as new ones, which were biochemically validated. The newly identified MYC targets include some major hubs. This approach can be generally useful for the analysis of normal and pathologic networks in mammalian cells.

Algorithms↗
PubMed2006

More than just 'doing the math'.

Two new articles show how computational tools continue to move beyond mere sequence-based bioinformatic analysis into more advanced arenas of prediction, deduction and network building.

Animals↗