J Am Med Inform Assoc - An integrated approach to identify causal network modules of complex diseases with application to colorectal cancer.

Tópicos

{ gene(2352) biolog(1181) express(1162) }
{ system(1976) rule(880) can(841) }
{ problem(2511) optim(1539) algorithm(950) }
{ data(3963) clinic(1234) research(1004) }
{ risk(3053) factor(974) diseas(938) }
{ studi(2440) review(1878) systemat(933) }
{ design(1359) user(1324) use(1319) }
{ can(774) often(719) complex(702) }
{ imag(2675) segment(2577) method(1081) }
{ visual(1396) interact(850) tool(830) }
{ model(2656) set(1616) predict(1553) }
{ data(3008) multipl(1320) sourc(1022) }
{ first(2504) two(1366) second(1323) }
{ result(1111) use(1088) new(759) }
{ treatment(1704) effect(941) patient(846) }
{ algorithm(1844) comput(1787) effici(935) }
{ general(901) number(790) one(736) }
{ studi(1410) differ(1259) use(1210) }
{ activ(1138) subject(705) human(624) }
{ can(981) present(881) function(850) }
{ high(1669) rate(1365) level(1280) }
{ cancer(2502) breast(956) screen(824) }
{ activ(1452) weight(1219) physic(1104) }
{ imag(1947) propos(1133) code(1026) }
{ data(1737) use(1416) pattern(1282) }
{ inform(2794) health(2639) internet(1427) }
{ measur(2081) correl(1212) valu(896) }
{ bind(1733) structur(1185) ligand(1036) }
{ sequenc(1873) structur(1644) protein(1328) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
{ assess(1506) score(1403) qualiti(1306) }
{ framework(1458) process(801) describ(734) }
{ howev(809) still(633) remain(590) }
{ research(1085) discuss(1038) issu(1018) }
{ system(1050) medic(1026) inform(1018) }
{ compound(1573) activ(1297) structur(1058) }
{ model(3480) simul(1196) paramet(876) }
{ state(1844) use(1261) util(961) }
{ process(1125) use(805) approach(778) }
{ model(3404) distribut(989) bayesian(671) }
{ imag(1057) registr(996) error(939) }
{ method(1219) similar(1157) match(930) }
{ network(2748) neural(1063) input(814) }
{ patient(2315) diseas(1263) diabet(1191) }
{ take(945) account(800) differ(722) }
{ motion(1329) object(1292) video(1091) }
{ surgeri(1148) surgic(1085) robot(1054) }
{ error(1145) method(1030) estim(1020) }
{ chang(1828) time(1643) increas(1301) }
{ learn(2355) train(1041) set(1003) }
{ concept(1167) ontolog(924) domain(897) }
{ clinic(1479) use(1117) guidelin(835) }
{ extract(1171) text(1153) clinic(932) }
{ method(1557) propos(1049) approach(1037) }
{ data(1714) softwar(1251) tool(1186) }
{ control(1307) perform(991) simul(935) }
{ model(2220) cell(1177) simul(1124) }
{ care(1570) inform(1187) nurs(1089) }
{ method(984) reconstruct(947) comput(926) }
{ search(2224) databas(1162) retriev(909) }
{ featur(1941) imag(1645) propos(1176) }
{ case(1353) use(1143) diagnosi(1136) }
{ perform(999) metric(946) measur(919) }
{ import(1318) role(1303) understand(862) }
{ model(2341) predict(2261) use(1141) }
{ perform(1367) use(1326) method(1137) }
{ studi(1119) effect(1106) posit(819) }
{ blood(1257) pressur(1144) flow(957) }
{ spatial(1525) area(1432) region(1030) }
{ record(1888) medic(1808) patient(1693) }
{ health(3367) inform(1360) care(1135) }
{ monitor(1329) mobil(1314) devic(1160) }
{ ehr(2073) health(1662) electron(1139) }
{ research(1218) medic(880) student(794) }
{ patient(2837) hospit(1953) medic(668) }
{ data(2317) use(1299) case(1017) }
{ age(1611) year(1155) adult(843) }
{ medic(1828) order(1363) alert(1069) }
{ signal(2180) analysi(812) frequenc(800) }
{ cost(1906) reduc(1198) effect(832) }
{ group(2977) signific(1463) compar(1072) }
{ sampl(1606) size(1419) use(1276) }
{ intervent(3218) particip(2042) group(1664) }
{ time(1939) patient(1703) rate(768) }
{ patient(1821) servic(1111) care(1106) }
{ use(2086) technolog(871) perceiv(783) }
{ analysi(2126) use(1163) compon(1037) }
{ health(1844) social(1437) communiti(874) }
{ structur(1116) can(940) graph(676) }
{ use(976) code(926) identifi(902) }
{ use(1733) differ(960) four(931) }
{ drug(1928) target(777) effect(648) }
{ implement(1333) system(1263) develop(1122) }
{ survey(1388) particip(1329) question(1065) }
{ estim(2440) model(1874) function(577) }
{ decis(3086) make(1611) patient(1517) }
{ method(1969) cluster(1462) data(1082) }
{ method(2212) result(1239) propos(1039) }
{ detect(2391) sensit(1101) algorithm(908) }

Resumo

CKGROUND: Many methods have been developed to identify disease genes and further module biomarkers of complex diseases based on gene expression data. It is generally difficult to distinguish whether the variations in gene expression are causative or merely the effect of a disease. The limitation of relying on gene expression data alone highlights the need to develop new approaches that can explore various data to reflect the casual relationship between network modules and disease traits.METHODS: In this work, we developed a novel network-based approach to identify putative causal module biomarkers of complex diseases by integrating heterogeneous information, for example, epigenomic data, gene expression data, and protein-protein interaction network. We first formulated the identification of modules as a mathematical programming problem, which can be solved efficiently and effectively in an accurate manner. Then, we applied our approach to colorectal cancer (CRC) and identified several network modules that can serve as potential module biomarkers for characterizing CRC. Further validations using three additional gene expression datasets verified their candidate biomarker properties and the effectiveness of the method. Functional enrichment analysis also revealed that the identified modules are strongly related to hallmarks of cancer, and the enriched functions, such as inflammatory response, receptor and signaling pathways, are specific to CRC.RESULTS: Through constructing a transcription factor (TF)-module network, we found that aberrant DNA methylation of genes encoding TF considerably contributes to the activity change of some genes, which may function as causal genes of CRC, and that can also be exploited to develop efficient therapies or effective drugs.CONCLUSION: Our method can potentially be extended to the study of other complex diseases and the multiclassification problem.

Resumo Limpo

ckground mani method develop identifi diseas gene modul biomark complex diseas base gene express data general difficult distinguish whether variat gene express causat mere effect diseas limit reli gene express data alon highlight need develop new approach can explor various data reflect casual relationship network modul diseas traitsmethod work develop novel networkbas approach identifi putat causal modul biomark complex diseas integr heterogen inform exampl epigenom data gene express data proteinprotein interact network first formul identif modul mathemat program problem can solv effici effect accur manner appli approach colorect cancer crc identifi sever network modul can serv potenti modul biomark character crc valid use three addit gene express dataset verifi candid biomark properti effect method function enrich analysi also reveal identifi modul strong relat hallmark cancer enrich function inflammatori respons receptor signal pathway specif crcresult construct transcript factor tfmodul network found aberr dna methyl gene encod tf consider contribut activ chang gene may function causal gene crc can also exploit develop effici therapi effect drugsconclus method can potenti extend studi complex diseas multiclassif problem

Resumos Similares

J. Comput. Biol. - Bioinformatics method to analyze the mechanism of pancreatic cancer disorder. ( 0,922633424230748 )
J Am Med Inform Assoc - Identifying disease genes and module biomarkers by differential interactions. ( 0,916625481340839 )
Wiley Interdiscip Rev Syst Biol Med - Diverse functional networks of Tbx3 in development and disease. ( 0,90967755153156 )
J Am Med Inform Assoc - Extracting coordinated patterns of DNA methylation and gene expression in ovarian cancer. ( 0,909226544230971 )
Brief. Bioinformatics - Revealing the architecture of genetic and epigenetic regulation: a maximum likelihood model. ( 0,905907662518161 )
J Integr Bioinform - An integrative bioinformatics framework for genome-scale multiple level network reconstruction of rice. ( 0,901043477213932 )
J. Comput. Biol. - Vavien: an algorithm for prioritizing candidate disease genes based on topological similarity of proteins in interaction networks. ( 0,899217903041951 )
Wiley Interdiscip Rev Syst Biol Med - Signaling networks in palate development. ( 0,898711473619138 )
Wiley Interdiscip Rev Syst Biol Med - miRNA regulation in the context of functional protein networks: principles and applications. ( 0,898194474570084 )
Comput. Biol. Med. - Identification and analysis of the regulatory network of Myc and microRNAs from high-throughput experimental data. ( 0,897556652715632 )
Comput Biol Chem - In silico analysis of cis-acting regulatory elements in 5' regulatory regions of sucrose transporter gene families in rice (Oryza sativa Japonica) and Arabidopsis thaliana. ( 0,896637484455891 )
Comput Math Methods Med - First comprehensive in silico analysis of the functional and structural consequences of SNPs in human GalNAc-T1 gene. ( 0,896069027514451 )
J Integr Bioinform - Assembling cell context-specific gene sets: a case in cardiomyopathy. ( 0,895856189781939 )
Comput Math Methods Med - Integrating gene expression and protein interaction data for signaling pathway prediction of Alzheimer's disease. ( 0,89567449570929 )
Artif Intell Med - Identifying regulatory relationships among genomic loci, biological pathways, and disease. ( 0,895614591952813 )
J Integr Bioinform - Knowledge enrichment analysis for human tissue-specific genes uncover new biological insights. ( 0,893899133824383 )
J. Comput. Biol. - A topology-based score for pathway enrichment. ( 0,892337599619316 )
J Integr Bioinform - Towards prediction and prioritization of disease genes by the modularity of human phenome-genome assembled network. ( 0,888958446477306 )
Brief. Bioinformatics - Identifying miRNAs, targets and functions. ( 0,886078965897592 )
Wiley Interdiscip Rev Syst Biol Med - Using a systems biology approach to understand and study the mechanisms of metastasis. ( 0,884740145167193 )
Artif Intell Med - An extensive analysis of disease-gene associations using network integration and fast kernel-based gene prioritization methods. ( 0,884033170602 )
Comput Biol Chem - Disruption of murine Tcte3-3 induces tissue specific apoptosis via co-expression of Anxa5 and Pebp1. ( 0,883459357008503 )
Comput Math Methods Med - Understanding the pathogenesis of Kawasaki disease by network and pathway analysis. ( 0,880241127125064 )
J Biomed Inform - The detection of risk pathways, regulated by miRNAs, via the integration of sample-matched miRNA-mRNA profiles and pathway structure. ( 0,87952172334671 )
Wiley Interdiscip Rev Syst Biol Med - Using variability in gene expression as a tool for studying gene regulation. ( 0,879411876328123 )
J Am Med Inform Assoc - Network models of genome-wide association studies uncover the topological centrality of protein interactions in complex diseases. ( 0,879119446806662 )
J. Comput. Biol. - An algorithm for efficient identification of branched metabolic pathways. ( 0,878428064176156 )
Wiley Interdiscip Rev Syst Biol Med - Postgenomic technologies targeting the Wnt signaling network. ( 0,877867663440218 )
Wiley Interdiscip Rev Syst Biol Med - Systems biology of adipose tissue metabolism: regulation of growth, signaling and inflammation. ( 0,87756048489934 )
J Integr Bioinform - Network expansion and pathway enrichment analysis towards biologically significant findings from microarrays. ( 0,874674823602408 )
Comput Biol Chem - Identifying novel prostate cancer associated pathways based on integrative microarray data analysis. ( 0,871028967751821 )
Wiley Interdiscip Rev Syst Biol Med - Regulatory variation: an emerging vantage point for cancer biology. ( 0,870655898464517 )
J Am Med Inform Assoc - Knowledge boosting: a graph-based integration approach with multi-omics data and genomic knowledge for cancer clinical outcome prediction. ( 0,86825535198474 )
J Biomed Inform - Prioritization of potential candidate disease genes by topological similarity of protein-protein interaction network and phenotype data. ( 0,866033178463642 )
Wiley Interdiscip Rev Syst Biol Med - Network biology: a direct approach to study biological function. ( 0,865380250943713 )
Comput. Biol. Med. - Mathematical modeling and sensitivity analysis of the integrated TNFa-mediated apoptotic pathway for identifying key regulators. ( 0,864692671553063 )
Wiley Interdiscip Rev Syst Biol Med - Reverse-engineering human regulatory networks. ( 0,864092897178542 )
Methods Inf Med - Pathway based microarray analysis, utilising enzyme compounds and cascade events. ( 0,860501139442171 )
J Biomed Inform - Independent component analysis: mining microarray data for fundamental human gene expression modules. ( 0,858464670776991 )
J Biomed Inform - Comparative analysis of a novel disease phenotype network based on clinical manifestations. ( 0,857901179426686 )
Comput Biol Chem - Using volcano plots and regularized-chi statistics in genetic association studies. ( 0,855667398272144 )
Brief. Bioinformatics - Identification of aberrant pathways and network activities from high-throughput data. ( 0,853723374914534 )
J Biomed Inform - Gene pathways and subnetworks distinguish between major glioma subtypes and elucidate potential underlying biology. ( 0,853539062631719 )
J Biomed Inform - A comparative study of covariance selection models for the inference of gene regulatory networks. ( 0,853350338647255 )
J Integr Bioinform - Predicting breast cancer chemotherapeutic response using a novel tool for microarray data analysis. ( 0,8528804035292 )
Wiley Interdiscip Rev Syst Biol Med - Recent advances in prostate development and links to prostatic diseases. ( 0,849250850842318 )
Comput. Biol. Med. - Degrees of separation as a statistical tool for evaluating candidate genes. ( 0,84905888925253 )
J Am Med Inform Assoc - Complex-disease networks of trait-associated single-nucleotide polymorphisms (SNPs) unveiled by information theory. ( 0,847731965638832 )
Sci Data - DNA methylation temporal profiling following peripheral versus central nervous system axotomy. ( 0,847140650260556 )
Wiley Interdiscip Rev Syst Biol Med - Sex and the circuitry: progress toward a systems-level understanding of vertebrate sex determination. ( 0,84435809246059 )
AMIA Annu Symp Proc - An ontology-neutral framework for enrichment analysis. ( 0,842749660422679 )
Comput Biol Chem - Bioinformatic analysis of molecular network of glucosinolate biosynthesis. ( 0,842082719215786 )
Brief. Bioinformatics - Targeted metabolic reconstruction: a novel approach for the characterization of plant-pathogen interactions. ( 0,841977761271239 )
AMIA Annu Symp Proc - Mining disease fingerprints from within genetic pathways. ( 0,841228835771039 )
Comput. Biol. Med. - A molecular prospective provides new insights into implication of PDYN and OPRK1 genes in alcohol dependence. ( 0,840877382875898 )
Comput Biol Chem - Expression patterns of photoperiod and temperature regulated heading date genes in Oryza sativa. ( 0,840613221621219 )
J Integr Bioinform - A study of the short and long-term regulation of E. coli metabolic pathways. ( 0,839628408211089 )
Comput Biol Chem - Using gene expression programming to infer gene regulatory networks from time-series data. ( 0,838850508765927 )
Comput Biol Chem - Statistical analysis of combinatorial transcriptional regulatory motifs in human intron-containing promoter sequences. ( 0,838334828010864 )
J. Comput. Biol. - Computational disease gene prioritization: an appraisal. ( 0,837224693293284 )
Comput Biol Chem - A computational method of predicting regulatory interactions in Arabidopsis based on gene expression data and sequence information. ( 0,837094587964905 )
Comput Biol Chem - Large-scale mining co-expressed genes in Arabidopsis anther: from pair to group. ( 0,836183802172044 )
Comput Biol Chem - Deciphering histone code of transcriptional regulation in malaria parasites by large-scale data mining. ( 0,833643341002556 )
Brief. Bioinformatics - Learning transcriptional regulation on a genome scale: a theoretical analysis based on gene expression data. ( 0,832805520131851 )
IEEE J Biomed Health Inform - Using evolutional properties of gene networks in understanding survival prognosis of glioblastoma. ( 0,83231293890217 )
Sci Data - Transcriptomic analysis of midbrain and individual hindbrain rhombomeres in the chick embryo. ( 0,83101408182118 )
Comput. Biol. Med. - Revealing pathway maps of renal cell carcinoma by gene expression change. ( 0,82890479170032 )
Wiley Interdiscip Rev Syst Biol Med - Cyclic nucleotide signaling in intestinal epithelia: getting to the gut of the matter. ( 0,828801766727629 )
Wiley Interdiscip Rev Syst Biol Med - Integrating omics into the cardiac differentiation of human pluripotent stem cells. ( 0,827864951842439 )
Comput. Biol. Med. - Meta analysis of gene expression changes upon treatment of A549 cells with anti-cancer drugs to identify universal responses. ( 0,826875732364112 )
Wiley Interdiscip Rev Syst Biol Med - The zebrafish: scalable in vivo modeling for systems biology. ( 0,822767325482312 )
Comput. Biol. Med. - A review on the computational approaches for gene regulatory network construction. ( 0,822719451501501 )
J Biomed Inform - Systems-based biological concordance and predictive reproducibility of gene set discovery methods in cardiovascular disease. ( 0,82239656127423 )
Comput Biol Chem - Sparse regularized discriminant analysis with application to microarrays. ( 0,821921668012933 )
Comput Math Methods Med - Identification and functional annotation of genome-wide ER-regulated genes in breast cancer based on ChIP-Seq data. ( 0,818579818825405 )
Comput. Biol. Med. - Discovering the transcriptional modules using microarray data by penalized matrix decomposition. ( 0,8173673128205 )
Comput. Biol. Med. - Computational gene network study on antibiotic resistance genes of Acinetobacter baumannii. ( 0,817222113741951 )
Brief. Bioinformatics - Evolution of gene regulation--on the road towards computational inferences. ( 0,817054021622985 )
Wiley Interdiscip Rev Syst Biol Med - Stem cell bioengineering at the interface of systems-based models and high-throughput platforms. ( 0,816816700479694 )
Comput Math Methods Med - Dynamic regulatory network reconstruction for Alzheimer's disease based on matrix decomposition techniques. ( 0,816485318907911 )
AMIA Annu Symp Proc - Towards mechanism classifiers: expression-anchored Gene Ontology signature predicts clinical outcome in lung adenocarcinoma patients. ( 0,814097829763013 )
J Biomed Inform - Protein interaction network underpins concordant prognosis among heterogeneous breast cancer signatures. ( 0,812928564454407 )
AMIA Annu Symp Proc - Similarity-based disease risk assessment for personal genomes: proof of concept. ( 0,81221957112553 )
Wiley Interdiscip Rev Syst Biol Med - Noncoding RNAs in gene regulation. ( 0,811059197146913 )
Comput Biol Chem - GPEC: a Cytoscape plug-in for random walk-based gene prioritization and biomedical evidence collection. ( 0,810436105874218 )
J Integr Bioinform - Uncovering the expression patterns of chimeric transcripts using surveys of affymetrix GeneChips. ( 0,810027787669851 )
Wiley Interdiscip Rev Syst Biol Med - Protein microarrays for genome-wide posttranslational modification analysis. ( 0,80868988907899 )
Comput Math Methods Med - Molecular signature of cancer at gene level or pathway level? Case studies of colorectal cancer and prostate cancer microarray data. ( 0,806498478333654 )
J Am Med Inform Assoc - Utility of gene-specific algorithms for predicting pathogenicity of uncertain gene variants. ( 0,805928256236233 )
Curr Protoc Bioinformatics - BEDTools: The Swiss-Army Tool for Genome Feature Analysis. ( 0,805917350109886 )
Wiley Interdiscip Rev Syst Biol Med - Mediators and dynamics of DNA methylation. ( 0,804783249282948 )
J Biomed Inform - Inferring cell cycle feedback regulation from gene expression data. ( 0,804054938122111 )
Wiley Interdiscip Rev Syst Biol Med - Where gene discovery turns into systems biology: genome-scale RNAi screens in Drosophila. ( 0,803491025427811 )
Brief. Bioinformatics - Apoptosis regulatory protein-protein interaction demonstrates hierarchical scale-free fractal network. ( 0,803446113358786 )
Sci Data - Genomes and phenomes of a population of outbred rats and its progenitors. ( 0,802749569728114 )
Comput Biol Chem - Identification of all trinucleotide circular codes. ( 0,802260480733569 )
J Integr Bioinform - Profiling of genetic switches using boolean implications in expression data. ( 0,801897750644364 )
Brief. Bioinformatics - Toward microRNA-mediated gene regulatory networks in plants. ( 0,800742550657608 )
Comput Biol Chem - Revealing weak differential gene expressions and their reproducible functions associated with breast cancer metastasis. ( 0,800152399159615 )
Methods Inf Med - Identification of breast cancer prognosis markers using integrative sparse boosting. ( 0,798181699175565 )