01819nas a2200265   4500008004100000022001400041245007700055210006900132260001600201300001400217490000700231520098400238653001501222653001101237653002301248653002401271653002001295653001801315100001901333700002201352700001801374700003101392700002001423856011001443       2019                        eng d  a1477-405400aA comparison of mechanistic signaling pathway activity analysis methods.0 acomparison of mechanistic signaling pathway activity analysis me  c2019 Sep 27  a1655-16680 v203 a<p>Understanding the aspects of cell functionality that account for disease mechanisms or drug modes of action is a main challenge for precision medicine. Classical gene-based approaches ignore the modular nature of most human traits, whereas conventional pathway enrichment approaches produce only illustrative results of limited practical utility. Recently, a family of new methods has emerged that change the focus from the whole pathways to the definition of elementary subpathways within them that have any mechanistic significance and to the study of their activities. Thus, mechanistic pathway activity (MPA) methods constitute a new paradigm that allows recoding poorly informative genomic measurements into cell activity quantitative values and relate them to phenotypes. Here we provide a review on the MPA methods available and explain their contribution to systems medicine approaches for addressing challenges in the diagnostic and treatment of complex diseases.</p>10aAlgorithms10aHumans10aPostmortem Changes10aSignal Transduction10aSystems biology10aTranscriptome1 aAmadoz, Alicia1 aHidalgo, Marta, R1 aCubuk, Cankut1 aCarbonell-Caballero, José1 aDopazo, Joaquin  uhttps://www.clinbioinfosspa.es/content/comparison-mechanistic-signaling-pathway-activity-analysis-methods02578nas a2200529   4500008004100000022001400041245008700055210006900142260001600211300000800227490000600235520103000241653001001271653001801281653001001299653001101309653002001320653001101340653002301351653002301374653001901397653002501416653001801441100002301459700002701482700002101509700002501530700001601555700001901571700001701590700002201607700002401629700003101653700002101684700002401705700001901729700002401748700001801772700001801790700002101808700002001829700002001849700002101869700002301890700002001913856011501933       2018                        eng d  a2041-172300aThe effects of death and post-mortem cold ischemia on human tissue transcriptomes.0 aeffects of death and postmortem cold ischemia on human tissue tr  c2018 Feb 13  a4900 v93 a<p>Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.</p>10aBlood10aCold Ischemia10aDeath10aFemale10agene expression10aHumans10aModels, Biological10aPostmortem Changes10aRNA, Messenger10aStochastic Processes10aTranscriptome1 aFerreira, Pedro, G1 aMuñoz-Aguirre, Manuel1 aReverter, Ferran1 aGodinho, Caio, P Sá1 aSousa, Abel1 aAmadoz, Alicia1 aSodaei, Reza1 aHidalgo, Marta, R1 aPervouchine, Dmitri1 aCarbonell-Caballero, José1 aNurtdinov, Ramil1 aBreschi, Alessandra1 aAmador, Raziel1 aOliveira, Patrícia1 aCubuk, Cankut1 aCurado, João1 aAguet, François1 aOliveira, Carla1 aDopazo, Joaquin1 aSammeth, Michael1 aArdlie, Kristin, G1 aGuigó, Roderic  uhttps://www.clinbioinfosspa.es/content/effects-death-and-post-mortem-cold-ischemia-human-tissue-transcriptomes