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Strong-association-rule mining for large-scale gene-expression data analysis: a case study on human SAGE data

GENOME BIOLOGY 2002年第12期3卷 research0067.1-research0067.16页

作者： Becquet, Celine Blachon, Sylvain Jeudy, Baptiste Boulicaut, Jean-Francois Gandrillon, Olivier Univ Lyon 1 Equipe Signalisat & Identites Cellulaires Ctr Genet Mol & Cellulaire CNRSUMR 5534 F-69622 Villeurbanne France Inst Natl Sci Appl Lab Ingn Syst Informat F-69621 Villeurbanne France

Background: The association-rules discovery (ARD) technique has yet to be applied to gene-expression data analysis. Even in the absence of previous biological knowledge, it should identify sets of genes whose expression is correlated. The first association-rule miners appeared six years ago and proved efficient at dealing with sparse and weakly correlated data. A huge international research effort has led to new algorithms for tackling difficult contexts and these are particularly suited to analysis of large gene-expression matrices. To validate the ARD technique we have applied it to freely available human serial analysis of gene expression (SAGE) data. Results: The approach described here enables us to designate sets of strong association rules. We normalized the SAGE data before applying our association rule miner. Depending on the discretization algorithm used, different properties of the data were highlighted. Both common and specific interpretations could be made from the extracted rules. In each and every case the extracted collections of rules indicated that a very strong co-regulation of mRNA encoding ribosomal proteins occurs in the dataset. Several rules associating proteins involved in signal transduction were obtained and analyzed, some pointing to yet-unexplored directions. Furthermore, by examining a subset of these rules, we were able both to reassign a wrongly labeled tag, and to propose a function for an expressed sequence tag encoding a protein of unknown function. Conclusions: We show that ARD is a promising technique that turns out to be complementary to existing gene-expression clustering techniques.

关键词： Association Rule additional data file Frequent Itemsets Association Rule Miner Frequency Threshold

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Reduced reliance on the trace element selenium during evolution of mammals

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GENOME BIOLOGY 2008年第3期9卷 R62-R62页

作者： Lobanov, Alexey V. Hatfield, Dolph L. Gladyshev, Vadim N. Univ Nebraska Dept Biochem Lincoln NE 68588 USA NCI Sect Mol Biol Selenium Lab Canc Prevent NIH Bethesda MD 20892 USA

Background Selenium (Se) is an essential trace element that occurs in proteins in the form of selenocysteine (Sec). It is transported throughout the body in the form of Sec residues in Selenoprotein P (SelP), a plasma protein of unclear origin recently proposed as an experimental marker of dietary Se status. Results Here, we report that the N-terminal domain of SelP is distantly related to ancestral bacterial thiol oxidoreductases of the thioredoxin superfamily, and that its C-terminal Se transport domain may have originated in early metazoan evolution by de novo accumulation of Sec residues. Reconstruction of evolutionary changes in the Se transport domain indicates a decrease in Sec content of SelP specifically in the mammalian lineage via replacement of Sec with cysteine (Cys). Sec content of mammalian SelPs varies more than two fold and is lowest in rodents and primates. Compared to mammals, fish show higher Sec content of SelP, larger selenoproteomes, elevated SelP gene expression, and higher levels of tissue Se. In addition, mammals replaced Sec with Cys in several proteins and lost several selenoproteins altogether, whereas such events are not found in fish. Conclusions These data suggest that evolution from fish to mammals was accompanied by decreased use of Sec and that analyses of SelP, selenoproteomes and Sec/Cys transitions provide a genetic marker of utilization of this trace element in vertebrates. The evolved reduced reliance on Se raises questions regarding the need to maximize selenoprotein expression by Se dietary supplements in situations when pathology is not imminent, a currently accepted practice.

关键词： additional data file Recommend Dietary Allowance Whole Genome Shotgun SECIS Element Selenoprotein Gene

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SPACE: an algorithm to predict and quantify alternatively spliced isoforms using microarrays

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GENOME BIOLOGY 2008年第2期9卷 R46-R46页

作者： Anton, Miguel A. Gorostiaga, Dorleta Guruceaga, Elizabeth Segura, Victor Carmona-Saez, Pedro Pascual-Montano, Alberto Pio, Ruben Montuenga, Luis M. Rubio, Angel Univ Navarra CEIT San Sebastian Spain Univ Navarra TECNUN San Sebastian Spain Integrom SL Madrid Spain Univ Complutense Madrid Fac Ciencias Fis Comp Architecture Dept E-28040 Madrid Spain Univ Navarra Dept Biochem E-31080 Pamplona Spain Univ Navarra Ctr Appl Med Res E-31080 Pamplona Spain Univ Navarra Dept Histol & Pathol E-31080 Pamplona Spain

Exon and exon+junction microarrays are promising tools to study alternative splicing (AS). Current analytical tools applied to these arrays lack two relevant features: ability to predict unknown spliced forms and quantify the concentration of known and unknown isoforms. SPACE is an algorithm developed to 1) estimate the number of different transcripts expressed in several conditions, 2) predict the pre-mRNA splicing structure and 3) quantify the transcript concentrations including unknown forms. Results show its robustness and accuracy for real and simulated data.

关键词： Reverse Transcription Polymerase Chain Reaction additional data file Multiplicative Noise Probe Expression Exon Cassette

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On the species of origin: diagnosing the source of symbiotic transcripts

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GENOME BIOLOGY 2001年第9期2卷 research0037.1-research0037.14页

作者： Hraber, Peter T. Weller, Jennifer W. Santa Fe Inst Santa Fe NM 87501 USA Virginia Bioinformat Inst Blacksburg VA 24061 USA

Background: Most organisms have developed ways to recognize and interact with other species. Symbiotic interactions range from pathogenic to mutualistic. Some molecular mechanisms of interspecific interaction are well understood, but many remain to be discovered. Expressed sequence tags (ESTs) from cultures of interacting symbionts can help identify transcripts that regulate symbiosis, but present a unique challenge for functional analysis. Given a sequence expressed in an interaction between two symbionts, the challenge is to determine from which organism the transcript originated. For high-throughput sequencing from interaction cultures, a reliable computational approach is needed. Previous investigations into GC nucleotide content and comparative similarity searching provide provisional solutions, but a comparative lexical analysis, which uses a likelihood-ratio test of hexamer counts, is more powerful. Results: Validation with genes whose origin and function are known yielded 94% accuracy. Microbial (non-plant) transcripts comprised 75% of a Phytophthora sojae-infected soybean (Glycine max cv Harasoy) library, contrasted with 15% or less in root tissue libraries of Medicago truncatula from axenic, Phytophthora medicaginis-infected, mycorrhizal, and rhizobacterial treatments. Mycorrhizal libraries contained about 23% microbial transcripts;an axenic plant library contained a similar proportion of putative microbial transcripts. Conclusions: Comparative lexical analysis offers numerous advantages over alternative approaches. Many of the transcripts isolated from mixed cultures were of unknown function, suggesting specificity to symbiotic metabolism and therefore candidates likely to be interesting for further functional investigation. Future investigations will determine whether the abundance of non-plant transcripts in a pure plant library indicates procedural artifacts, horizontally transferred genes, or other phenomena.

关键词： Codon Usage additional data file Training Sequence Word Counting Lexical Analysis

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New genes in the evolution of the neural crest differentiation program

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GENOME BIOLOGY 2007年第3期8卷 R36-R36页

作者： Martinez-Morales, Juan-Ramon Henrich, Thorsten Ramialison, Mirana Wittbrodt, Joachim European Mol Biol Lab Dev Biol Unit D-69117 Heidelberg Germany

Background: Development of the vertebrate head depends on the multipotency and migratory behavior of neural crest derivatives. This cell population is considered a vertebrate innovation and, accordingly, chordate ancestors lacked neural crest counterparts. The identification of neural crest specification genes expressed in the neural plate of basal chordates, in addition to the discovery of pigmented migratory cells in ascidians, has challenged this hypothesis. These new findings revive the debate on what is new and what is ancient in the genetic program that controls neural crest formation. Results: To determine the origin of neural crest genes, we analyzed Phenotype Ontology annotations to select genes that control the development of this tissue. Using a sequential blast pipeline, we phylogenetically classified these genes, as well as those associated with other tissues, in order to define tissue-specific profiles of gene emergence. Of neural crest genes, 9% are vertebrate innovations. Our comparative analyses show that, among different tissues, the neural crest exhibits a particularly high rate of gene emergence during vertebrate evolution. A remarkable proportion of the new neural crest genes encode soluble ligands that control neural crest precursor specification into each cell lineage, including pigmented, neural, glial, and skeletal derivatives. Conclusion: We propose that the evolution of the neural crest is linked not only to the recruitment of ancestral regulatory genes but also to the emergence of signaling peptides that control the increasingly complex lineage diversification of this plastic cell population.

关键词： Gene Ontology Neural Crest additional data file Neural Crest Cell Pfam Domain

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The microbial selenoproteome of the Sargasso Sea

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GENOME BIOLOGY 2005年第4期6卷 R37-R37页

作者： Zhang, Y Fomenko, DE Gladyshev, VN Univ Nebraska Dept Biochem Lincoln NE 68588 USA

Background: Selenocysteine ( Sec) is a rare amino acid which occurs in proteins in major domains of life. It is encoded by TGA, which also serves as the signal for termination of translation, precluding identification of selenoprotein genes by available annotation tools. Information on full sets of selenoproteins ( selenoproteomes) is essential for understanding the biology of selenium. Herein, we characterized the selenoproteome of the largest microbial sequence dataset, the Sargasso Sea environmental genome project. Results: We identified 310 selenoprotein genes that clustered into 25 families, including 101 new selenoprotein genes that belonged to 15 families. Most of these proteins were predicted redox proteins containing catalytic selenocysteines. Several bacterial selenoproteins previously thought to be restricted to eukaryotes were detected by analyzing eukaryotic and bacterial SECIS elements, suggesting that eukaryotic and bacterial selenoprotein sets partially overlapped. The Sargasso Sea microbial selenoproteome was rich in selenoproteins and its composition was different from that observed in the combined set of completely sequenced genomes, suggesting that these genomes do not accurately represent the microbial selenoproteome. Most detected selenoproteins occurred sporadically compared to the widespread presence of their cysteine homologs, suggesting that many selenoproteins recently evolved from cysteine-containing homologs. Conclusions: This study yielded the largest selenoprotein dataset to date, doubled the number of prokaryotic selenoprotein families and provided insights into forces that drive selenocysteine evolution.

关键词： additional data file Prokaryotic Genome SECIS Element Arsenate Reductase Selenoprotein Gene

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Explicit equilibrium modeling of transcription-factor binding and gene regulation

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GENOME BIOLOGY 2005年第10期6卷 R87-R87页

作者： Granek, JA Clarke, ND Johns Hopkins Univ Sch Med Dept Biophys & Biophys Chem Baltimore MD 21205 USA Natl Evolutionary Synth Ctr Durham NC 27705 USA Genome Inst Singapore Singapore 138672 Singapore

We have developed a computational model that predicts the probability of transcription factor binding to any site in the genome. GOMER (generalizable occupancy model of expression regulation) calculates binding probabilities on the basis of position weight matrices, and incorporates the effects of cooperativity and competition by explicit calculation of coupled binding equilibria. GOMER can be used to test hypotheses regarding gene regulation that build upon this physically principled prediction of protein-DNA binding.

关键词： Receiver Operating Characteristic Curve additional data file Competitive Interaction Cooperative Interaction Position Weight Matrix

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RNA editing of human microRNAs

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GENOME BIOLOGY 2006年第4期7卷 R27-R27页

作者： Blow, Matthew J. Grocock, Russell J. van Dongen, Stijn Enright, Anton J. Dicks, Ed Futreal, P. Andrew Wooster, Richard Stratton, Michael R. Wellcome Trust Sanger Inst Canc Genome Project Cambridge CB10 1SA England Inst Canc Res Sect Canc Genet Sutton SM2 5NG Surrey England

Background: MicroRNAs ( miRNAs) are short RNAs of around 22 nucleotides that regulate gene expression. The primary transcripts of miRNAs contain double-stranded RNA and are therefore potential substrates for adenosine to inosine (A- to- I) RNA editing. Results: We have conducted a survey of RNA editing of miRNAs from ten human tissues by sequence comparison of PCR products derived from matched genomic DNA and total cDNA from the same individual. Six out of 99 ( 6%) miRNA transcripts from which data were obtained were subject to A- to- I editing in at least one tissue. Four out of seven edited adenosines were in the mature miRNA and were predicted to change the target sites in 3' untranslated regions. For a further six miRNAs, we identified A- to- I editing of transcripts derived from the opposite strand of the genome to the annotated miRNA. These miRNAs may have been annotated to the wrong genomic strand. Conclusion: Our results indicate that RNA editing increases the diversity of miRNAs and their targets, and hence may modulate miRNA function.

关键词： additional data file miRNA Sequence Opposite Strand Editing Site Human miRNAs

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Design principles of molecular networks revealed by global comparisons and composite motifs

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GENOME BIOLOGY 2006年第7期7卷 R55-R55页

作者： Yu, Haiyuan Xia, Yu Trifonov, Valery Gerstein, Mark Yale Univ Dept Mol Biophys & Biochem New Haven CT 06520 USA

Background: Molecular networks are of current interest, particularly with the publication of many large-scale datasets. Previous analyses have focused on topologic structures of individual networks. Results: Here, we present a global comparison of four basic molecular networks: regulatory, co-expression, interaction, and metabolic. In terms of overall topologic correlation - whether nearby proteins in one network are close in another - we find that the four are quite similar. However, focusing on the occurrence of local features, we introduce the concept of composite hubs, namely hubs shared by more than one network. We find that the three 'action' networks (metabolic, co-expression, and interaction) share the same scaffolding of hubs, whereas the regulatory network uses distinctly different regulator hubs. Finally, we examine the inter-relationship between the regulatory network and the three action networks, focusing on three composite motifs - triangles, trusses, and bridges - involving different degrees of regulation of gene pairs. Our analysis shows that interaction and co-expression networks have short-range relationships, with directly interacting and co-expressed proteins sharing regulators. However, the metabolic network contains many long-distance relationships: far-away enzymes in a pathway often have time-delayed expression relationships, which are well coordinated by bridges connecting their regulators. Conclusion: We demonstrate how basic molecular networks are distinct yet connected and well coordinated. Many of our conclusions can be mapped onto structured social networks, providing intuitive comparisons. In particular, the long-distance regulation in metabolic networks agrees with its counterpart in social networks (namely, assembly lines). Conversely, the segregation of regulator hubs from other hubs diverges from social intuitions (as managers often are centers of interactions).

关键词： Regulatory Network Metabolic Network Assembly Line Action Network additional data file

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Evidence for horizontal transfer of a secondary metabolite gene cluster between fungi

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GENOME BIOLOGY 2008年第1期9卷 R18-R18页

作者： Khaldi, Nora Collemare, Jerome Lebrun, Marc-Henri Wolfe, Kenneth H. Univ Dublin Trinity Coll Smurfit Inst Genet Dublin 2 Ireland BCS INSA UCB UMR CNRS 5240 F-69263 Lyon 09 France

Background: Filamentous fungi synthesize many secondary metabolites and are rich in genes encoding proteins involved in their biosynthesis. Genes from the same pathway are often clustered and co-expressed in particular conditions. Such secondary metabolism gene clusters evolve rapidly through multiple rearrangements, duplications and losses. It has long been suspected that clusters can be transferred horizontally between species, but few concrete examples have been described so far. Results: In the rice blast fungus Magnaporthe grisea, the avirulence gene ACEI that codes for a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) belongs to a cluster of 15 genes involved in secondary metabolism. additional related clusters were detected in the ascomycetes Chaetomium globosum, Stagonospora nodorum and Aspergillus clavatus. Gene-by-gene phylogenetic analysis showed that in C. globosum and M. grisea, the evolution of these ACEI-like clusters is characterized by successive complex duplication events including tandem duplication within the M. grisea cluster. The phylogenetic trees also present evidence that at least five of the six genes in the homologous ACEI gene cluster in A. clavatus originated by horizontal transfer from a donor closely related to M. grisea. Conclusion: The ACEI cluster originally identified in M. grisea is shared by only few fungal species. Its sporadic distribution within euascomycetes is mainly explained by multiple events of duplication and losses. However, because A. clavatus contains an ACEI cluster of only six genes, we propose that horizontal transfer from a relative of M. grisea into an ancestor of A. clavatus provides a much simpler explanation of the observed data than the alternative of multiple events of duplication and losses of parts of the cluster.

关键词： Horizontal Gene Transfer additional data file Tandem Duplication Rice Blast Fungus Chaetomium Globosum

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