Pan-Cancer landscape of protein activities identifies drivers of signalling dysregulation and patient survival.

Genetic alterations in cancer cells trigger oncogenic transformation, a process largely mediated by the dysregulation of kinase and transcription factor (TF) activities. While the mutational profiles of thousands of tumours have been extensively characterised, the measurements of protein activities have been technically limited until recently. We compiled public data of matched genomics and (phospho)proteomics measurements for 1,110 tumours and 77 cell lines that we used to estimate activity changes in 218 kinases and 292 TFs.

PHONEMeS: Efficient Modeling of Signaling Networks Derived from Large-Scale Mass Spectrometry Data.

Post-translational modifications of proteins play an important role in the regulation of cellular processes. The mass spectrometry analysis of proteome modifications offers huge potential for the study of how protein inhibitors affect the phosphosignaling mechanisms inside the cells. We have recently proposed PHONEMeS, a method that uses high-content shotgun phosphoproteomic data to build logical network models of signal perturbation flow.

Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses.

Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Various tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolomics datasets.

Gender Differential Transcriptome in Gastric and Thyroid Cancers.

Cancer has an important and considerable gender differential susceptibility confirmed by several epidemiological studies. Gastric (GC) and thyroid cancer (TC) are examples of malignancies with a higher incidence in males and females, respectively. Beyond environmental predisposing factors, it is expected that gender-specific gene deregulation contributes to this differential incidence.

Gene Expression Analyses in Non Muscle Invasive Bladder Cancer Reveals a Role for Alternative Splicing and Tp53 Status.

Non-muscle invasive bladder cancer (NMIBC) represents a crucial problem for the national health care systems due to its high rates of recurrence and the consequent need of frequent follow-ups. Here, gene expression analyses in patients diagnosed as NMIBC were performed to determine those molecular pathways involved in tumor initiation, finding that both MYC and E2F are up regulated and helps to tumor initiation and progression. Our results also support an important involvement of alternative splicing events, modifying key pathways to favour bladder tumor evolution.

Multi-omics Characterization of Interaction-mediated Control of Human Protein Abundance levels.

Proteogenomic studies of cancer samples have shown that copy-number variation can be attenuated at the protein level for a large fraction of the proteome, likely due to the degradation of unassembled protein complex subunits. Such interaction-mediated control of protein abundance remains poorly characterized. To study this, we compiled genomic, (phospho)proteomic and structural data for hundreds of cancer samples and find that up to 42% of 8,124 analyzed proteins show signs of post-transcriptional control.

CDH1 somatic alterations in Mexican patients with diffuse and mixed sporadic gastric cancer.

Background: Diffuse gastric cancer (DGC) is associated with the reduction or absence of the expression of the cell adhesion protein E-cadherin (encoded by the CDH1 gene). Molecular characteristics are less well described for mixed gastric cancer (MGC). The main somatic alterations that have been described in the CDH1 gene are mutations, loss of heterozygosity (LOH) and promoter methylation.