@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 02 13}, pages = {490}, abstract = {

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.

}, 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} } @article {407, title = {The modular network structure of the mutational landscape of Acute Myeloid Leukemia.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0202926}, abstract = {

Acute myeloid leukemia (AML) is associated with the sequential accumulation of acquired genetic alterations. Although at diagnosis cytogenetic alterations are frequent in AML, roughly 50\% of patients present an apparently normal karyotype (NK), leading to a highly heterogeneous prognosis. Due to this significant heterogeneity, it has been suggested that different molecular mechanisms may trigger the disease with diverse prognostic implications. We performed whole-exome sequencing (WES) of tumor-normal matched samples of de novo AML-NK patients lacking mutations in NPM1, CEBPA or FLT3-ITD to identify new gene mutations with potential prognostic and therapeutic relevance to patients with AML. Novel candidate-genes, together with others previously described, were targeted resequenced in an independent cohort of 100 de novo AML patients classified in the cytogenetic intermediate-risk (IR) category. A mean of 4.89 mutations per sample were detected in 73 genes, 35 of which were mutated in more than one patient. After a network enrichment analysis, we defined a single in silico model and established a set of seed-genes that may trigger leukemogenesis in patients with normal karyotype. The high heterogeneity of gene mutations observed in AML patients suggested that a specific alteration could not be as essential as the interaction of deregulated pathways.

}, keywords = {Adult, Aged, Cytodiagnosis, Female, Gene Regulatory Networks, Genetic Association Studies, Genetic Heterogeneity, Humans, Karyotype, Leukemia, Myeloid, Acute, Male, Middle Aged, mutation, Neoplasm Proteins, Nucleophosmin, Prognosis, whole exome sequencing}, issn = {1932-6203}, doi = {10.1371/journal.pone.0202926}, author = {Ib{\'a}{\~n}ez, Mariam and Carbonell-Caballero, Jos{\'e} and Such, Esperanza and Garc{\'\i}a-Alonso, Luz and Liquori, Alessandro and L{\'o}pez-Pav{\'\i}a, Mar{\'\i}a and LLop, Marta and Alonso, Carmen and Barrag{\'a}n, Eva and G{\'o}mez-Segu{\'\i}, In{\'e}s and Neef, Alexander and Herv{\'a}s, David and Montesinos, Pau and Sanz, Guillermo and Sanz, Miguel Angel and Dopazo, Joaquin and Cervera, Jos{\'e}} } @article {483, title = {Sequencing and functional analysis of the genome of a nematode egg-parasitic fungus, Pochonia chlamydosporia.}, journal = {Fungal Genet Biol}, volume = {65}, year = {2014}, month = {2014 Apr}, pages = {69-80}, abstract = {

Pochonia chlamydosporia is a worldwide-distributed soil fungus with a great capacity to infect and destroy the eggs and kill females of plant-parasitic nematodes. Additionally, it has the ability to colonize endophytically roots of economically-important crop plants, thereby promoting their growth and eliciting plant defenses. This multitrophic behavior makes P. chlamydosporia a potentially useful tool for sustainable agriculture approaches. We sequenced and assembled \~{}41 Mb of P. chlamydosporia genomic DNA and predicted 12,122 gene models, of which many were homologous to genes of fungal pathogens of invertebrates and fungal plant pathogens. Predicted genes (65\%) were functionally annotated according to Gene Ontology, and 16\% of them found to share homology with genes in the Pathogen Host Interactions (PHI) database. The genome of this fungus is highly enriched in genes encoding hydrolytic enzymes, such as proteases, glycoside hydrolases and carbohydrate esterases. We used RNA-Seq technology in order to identify the genes expressed during endophytic behavior of P. chlamydosporia when colonizing barley roots. Functional annotation of these genes showed that hydrolytic enzymes and transporters are expressed during endophytism. This structural and functional analysis of the P. chlamydosporia genome provides a starting point for understanding the molecular mechanisms involved in the multitrophic lifestyle of this fungus. The genomic information provided here should also prove useful for enhancing the capabilities of this fungus as a biocontrol agent of plant-parasitic nematodes and as a plant growth-promoting organism.

}, keywords = {Animals, Ascomycota, Female, Gene Expression Regulation, Fungal, Gene ontology, Genome, Fungal, Hordeum, Host-Pathogen Interactions, Nematoda, Ovum, Phylogeny, Plant Roots, Sequence Analysis, DNA, Signal Transduction, Transcriptome}, issn = {1096-0937}, doi = {10.1016/j.fgb.2014.02.002}, author = {Larriba, Eduardo and Jaime, Mar{\'\i}a D L A and Carbonell-Caballero, Jos{\'e} and Conesa, Ana and Dopazo, Joaquin and Nislow, Corey and Mart{\'\i}n-Nieto, Jos{\'e} and Lopez-Llorca, Luis Vicente} }