Project description:HIF-metagene identifies hypoxic or constitutive HIF activation in scRNA-seq. Hypoxic normal cells have higher HIF-metagene scores than normoxic normal cells, and ccRCC tumour cells (harbouring VHL inactivation) have higher HIF-metagene score than normal cells.
Project description:Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype and the lack of specific signature makes difficult the development of targeted therapeutic strategy. We previously found that PRICKLE1, an evolutionary conserved protein acting as a regulator of vertebrate development, is upregulated in TNBC. Proteomic approaches allowed us to decipher the protein complex associated to PRICKLE1 in TNBC. Within that complex, we identified a large subset of proteins involved in the regulation of Rho-GTPase family members. We build a metagene with regulators of small G-protein activity and we found that this metagene is overexpressed in TNBC and is a poor prognosis marker. We analyzed the combination of the metagene expression and PRICKLE1 expression and identified that combined expression of ECT2 and PRICKLE1 provides a worst prognosis than PRICKLE1 expression alone in TNBC. ECT2 is a GEF for Rac1 and we showed that PRICKLE1 regulate the enzymatic activity of ECT2. Finally, we also observed that Ect2 and Prickle1 are functionally connected during evolution since both act synergistically to coordinate cellular movement during vertebrate gastrulation. Our results demonstrate the pivotal role of PRICKLE1 in TNBC and build the path for development of targeted therapeutic strategies to heal TNBC patients.
Project description:ChIP-seq was performed to profile H4R3me2a occupancy in HCT116 colorectal cancer cells with matched input DNA control. Libraries were sequenced as paired-end 150 bp reads on an Illumina NovaSeq 6000. Reads were aligned to GRCh38 with Bowtie2, peaks were called with MACS2 (q < 0.05), and metagene profiles were generated with deepTools.
Project description:We identified and validated the pivotal role for a metagene containing IFN-induced genes in association to higher metastatic potential as a function of the specific molecular subtype
Project description:We isolated nuclear mRNPs from yeast using an endogenous bi-molecular tagging approach on Sub2 and Hpr1. To validate the nature of these isolated particles, extracted RNA was sequenced and differential enrichment, as well as metagene coverage analysis were performed.