@article {695,
	title = {Mechanistic Models of Signaling Pathways Reveal the Drug Action Mechanisms behind Gender-Specific Gene Expression for Cancer Treatments.},
	journal = {Cells},
	volume = {9},
	year = {2020},
	month = {2020 06 29},
	abstract = {<p>Despite the existence of differences in gene expression across numerous genes between males and females having been known for a long time, these have been mostly ignored in many studies, including drug development and its therapeutic use. In fact, the consequences of such differences over the disease mechanisms or the drug action mechanisms are completely unknown. Here we applied mechanistic mathematical models of signaling activity to reveal the ultimate functional consequences that gender-specific gene expression activities have over cell functionality and fate. Moreover, we also used the mechanistic modeling framework to simulate the drug interventions and unravel how drug action mechanisms are affected by gender-specific differential gene expression. Interestingly, some cancers have many biological processes significantly affected by these gender-specific differences (e.g., bladder or head and neck carcinomas), while others (e.g., glioblastoma or rectum cancer) are almost insensitive to them. We found that many of these gender-specific differences affect cancer-specific pathways or in physiological signaling pathways, also involved in cancer origin and development. Finally, mechanistic models have the potential to be used for finding alternative therapeutic interventions on the pathways targeted by the drug, which lead to similar results compensating the downstream consequences of gender-specific differences in gene expression.</p>},
	keywords = {Female, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasms, Signal Transduction},
	issn = {2073-4409},
	doi = {10.3390/cells9071579},
	author = {Cubuk, Cankut and Can, Fatma E and Pe{\~n}a-Chilet, Maria and Dopazo, Joaquin}
}
@article {397,
	title = {The effects of death and post-mortem cold ischemia on human tissue transcriptomes.},
	journal = {Nat Commun},
	volume = {9},
	year = {2018},
	month = {2018 Feb 13},
	pages = {490},
	abstract = {<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>},
	keywords = {Blood, Cold Ischemia, Death, Female, gene expression, Humans, Models, Biological, Postmortem Changes, RNA, Messenger, Stochastic Processes, Transcriptome},
	issn = {2041-1723},
	doi = {10.1038/s41467-017-02772-x},
	author = {Ferreira, Pedro G and Mu{\~n}oz-Aguirre, Manuel and Reverter, Ferran and S{\'a} Godinho, Caio P and Sousa, Abel and Amadoz, Alicia and Sodaei, Reza and Hidalgo, Marta R and Pervouchine, Dmitri and Carbonell-Caballero, Jos{\'e} and Nurtdinov, Ramil and Breschi, Alessandra and Amador, Raziel and Oliveira, Patr{\'\i}cia and Cubuk, Cankut and Curado, Jo{\~a}o and Aguet, Fran{\c c}ois and Oliveira, Carla and Dopazo, Joaquin and Sammeth, Michael and Ardlie, Kristin G and Guig{\'o}, Roderic}
}
