Wiley Interdiscip Rev Syst Biol Med - Genome network medicine: innovation to overcome huge challenges in cancer therapy.

Tópicos

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{ research(1085) discuss(1038) issu(1018) }
{ sequenc(1873) structur(1644) protein(1328) }
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{ search(2224) databas(1162) retriev(909) }
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{ howev(809) still(633) remain(590) }
{ visual(1396) interact(850) tool(830) }
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{ health(3367) inform(1360) care(1135) }
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{ patient(1821) servic(1111) care(1106) }
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{ can(981) present(881) function(850) }
{ cancer(2502) breast(956) screen(824) }
{ method(2212) result(1239) propos(1039) }
{ can(774) often(719) complex(702) }
{ featur(3375) classif(2383) classifi(1994) }
{ imag(2830) propos(1344) filter(1198) }
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{ framework(1458) process(801) describ(734) }
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{ clinic(1479) use(1117) guidelin(835) }
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{ model(2220) cell(1177) simul(1124) }
{ care(1570) inform(1187) nurs(1089) }
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{ featur(1941) imag(1645) propos(1176) }
{ data(3963) clinic(1234) research(1004) }
{ risk(3053) factor(974) diseas(938) }
{ perform(999) metric(946) measur(919) }
{ system(1050) medic(1026) inform(1018) }
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{ monitor(1329) mobil(1314) devic(1160) }
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{ state(1844) use(1261) util(961) }
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{ age(1611) year(1155) adult(843) }
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{ cost(1906) reduc(1198) effect(832) }
{ group(2977) signific(1463) compar(1072) }
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Resumo

The post-ENCODE era shapes now a new biomedical research direction for understanding transcriptional and signaling networks driving gene expression and core cellular processes such as cell fate, survival, and apoptosis. Over the past half century, the Francis Crick 'central dogma' of single n gene/protein-phenotype (trait/disease) has defined biology, human physiology, disease, diagnostics, and drugs discovery. However, the ENCODE project and several other genomic studies using high-throughput sequencing technologies, computational strategies, and imaging techniques to visualize regulatory networks, provide evidence that transcriptional process and gene expression are regulated by highly complex dynamic molecular and signaling networks. This Focus article describes the linear experimentation-based limitations of diagnostics and therapeutics to cure advanced cancer and the need to move on from reductionist to network-based approaches. With evident a wide genomic heterogeneity, the power and challenges of next-generation sequencing (NGS) technologies to identify a patient's personal mutational landscape for tailoring the best target drugs in the individual patient are discussed. However, the available drugs are not capable of targeting aberrant signaling networks and research on functional transcriptional heterogeneity and functional genome organization is poorly understood. Therefore, the future clinical genome network medicine aiming at overcoming multiple problems in the new fields of regulatory DNA mapping, noncoding RNA, enhancer RNAs, and dynamic complexity of transcriptional circuitry are also discussed expecting in new innovation technology and strong appreciation of clinical data and evidence-based medicine. The problematic and potential solutions in the discovery of next-generation, molecular, and signaling circuitry-based biomarkers and drugs are explored.

Resumo Limpo

postencod era shape now new biomed research direct understand transcript signal network drive gene express core cellular process cell fate surviv apoptosi past half centuri franci crick central dogma singl n geneproteinphenotyp traitdiseas defin biolog human physiolog diseas diagnost drug discoveri howev encod project sever genom studi use highthroughput sequenc technolog comput strategi imag techniqu visual regulatori network provid evid transcript process gene express regul high complex dynam molecular signal network focus articl describ linear experimentationbas limit diagnost therapeut cure advanc cancer need move reductionist networkbas approach evid wide genom heterogen power challeng nextgener sequenc ngs technolog identifi patient person mutat landscap tailor best target drug individu patient discuss howev avail drug capabl target aberr signal network research function transcript heterogen function genom organ poor understood therefor futur clinic genom network medicin aim overcom multipl problem new field regulatori dna map noncod rna enhanc rnas dynam complex transcript circuitri also discuss expect new innov technolog strong appreci clinic data evidencebas medicin problemat potenti solut discoveri nextgener molecular signal circuitrybas biomark drug explor

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