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Integrative analysis of human protein, function, and disease networks 汇报人:周紫维 时 间:10.22 Protein-protein interaction (PPI) networks protein functions protein-pathway associations disease-gene 、 disease-disease associations Lack the data integration and analysis lack the strategy for integration the interrelated relationships-poorly investigated Method Protein module topological module function module disease module Method Method Protein networks Process : HIPPIE、IRefWeb Data :1830(P) ,2484(I) NeTA (Network topology algorithm) Results : 136 large & 185 small modules Topological Modules numbers : 136 1390(P:76%),2228(I:89.7%) ,M odularity:0.91385 Method Function Networks Protein-function network • Connect proteins with functions(three type) • Nodes : proteins , genes • Edges : significant association Protein-pathway network • Connect proteins with pathway annotations • DAVID : identify pathway enrichment Method Functional Modules • Principle : at least one function can cover all • Numbers : 136 Method Disease Networks Disease-gene networks Disease-Disease networks Tools OMIM (Online Mendelian Inheritance in Man) GWAS (Genome-wide association studies) Method Disease Modules Detect it based on disease-gene associations 15 kinds of diseases More than two proteins numbers : 139 Method Integrative Analysis annotate protein modules • disease-overlap-functional ----non-trivial • disease-overlap-pathway ----significant results : 69(non-) , 47(s) Analysis of integration Analysis of integration Analysis of integration Analysis of integration Analysis of integration Example topological module 3 Analysis of integration Example topological module 51 Comparison Compare with existing methods Markov Cluster Algorithm (MCL) default settings ,inflation parameter r=2 Random walker (RW) probability r = 0.4 NeTA Results The quality of the topological modules Finding and evaluating community structure in networks ---calculate modularity Results Three kinds of modules Results non-trivial protein modules & significant protein modules Systematic evaluation analysis A benchmark network database : OMIM & MIPS human complex construct a network • filter : 1460(P) , 4107(I) • at least one disease gene in each interactions • disease/protein/disease-prot ein complex Results The quality of the topological modules Results The numbers of three kind modules Results The mapping frequency of topological modules Summary Reference • http://www.micans.org/mcl/ • http://download.csdn.net/download/wsworl f/5212020/ • http://www.nature.com/articles/srep05739? WT.ec_id=SREP-20140722 • http://journals.aps.org/pre/abstract/10.1103 /PhysRevE.69.026113 • http://bioinformatics.oxfordjournals.org/con tent/21/16/3448.short • http://www.nature.com/nprot/journal/v4/n1 /abs/nprot.2008.211.html • …… Skip-thought vectors Skip-thought model Vocabulary expansion Skip-thought vectors RNN Skip-thought vectors RNN Gated Recurrent Unit Recurrent Neural Networks (GRU) ●距离加权,距离越大,权值越小 ●更新权重时,只对对应的单词更新 Skip-thought vectors Task ▪ 1.Semantic relatedness ▪ 2.Paragraph detection ▪ 3.Image-sentence ranking ▪ 4.Classification benchmarks 1.movie reviews sentiment 2.customer product reviews 3.subjectivety/objectivity classification 4.opinion polarity 5.question-type classification Skip-thought vectors Reference ▪ 1. Recurrent neural network based language model ▪ 2. Extensions of Recurrent neural network based language model ▪ 3. Generating Text with Recurrent Neural Networks ▪ http://blog.csdn.net/heyongluoyao8/article/ details/48636251 ▪ http://www.cnblogs.com/tornadomeet/p/34 39503.html