Project description:In this comprehensive study, the authors have developed concise models integrating clinical, genomic and transcriptomic features to predict intrinsic resistance to anti-PD1 Immune Checkpoint Blockade (ICB) treatment in individual tumors. It's important to note that their validation was performed in smaller, independent cohorts, constrained by data availability. The authors have developed two Logistic Regression based models for Ipilimumab treated and Ipilimumab naive patients with metastatic melanoma. The main predictive features for the Ipilimumab treated patients are MHC-II HLA, LDH at treatment initiation and the presence of lymph node metastases (LN met), chosen using forward selection methodology. The main predictive features for the Ipilimumab naive patients are tumor heterogeneity, tumor ploidy and tumor purity, chosen using forward selection methodology.
Please note that in these models, the output ‘1’ means progressive disease (PD) and ‘0’ means non-PD. The original GitHub repository can be accessed at https://github.com/vanallenlab/schadendorf-pd1
Project description:Analyses of new genomic, transcriptomic or proteomic data commonly result in trashing many unidentified data escaping the ‘canonical’ DNA-RNA-protein scheme. Testing systematic exchanges of nucleotides over long stretches produces inversed RNA pieces (here named “swinger” RNA) differing from their template DNA. These may explain some trashed data. Here analyses of genomic, transcriptomic and proteomic data of the pathogenic Tropheryma whipplei according to canonical genomic, transcriptomic and translational 'rules' resulted in trashing 58.9% of DNA, 37.7% RNA and about 85% of mass spectra (corresponding to peptides). In the trash, we found numerous DNA/RNA fragments compatible with “swinger” polymerization. Genomic sequences covered by «swinger» DNA and RNA are 3X more frequent than expected by chance and explained 12.4 and 20.8% of the rejected DNA and RNA sequences, respectively. As for peptides, several match with “swinger” RNAs, including some chimera, translated from both regular, and «swinger» transcripts, notably for ribosomal RNAs. Congruence of DNA, RNA and peptides resulting from the same swinging process suggest that systematic nucleotide exchanges increase coding potential, and may add to evolutionary diversification of bacterial populations.