Enhancing Mass Spectrometry-Based MHC-I Peptide Identification Through a Targeted Database Search Approach

MHC-bound peptide ligands dictate the activation and specificity of CD8+ T- cells-based and thus are important for devising T-cell immunotherapies. In recent times, advances in mass spectrometry (MS) have enabled the precise identification of these peptides, wherein MS/MS spectra are compared against a reference proteome. Unfortunately, matching immunopeptide MS/MS to reference proteome databases is hindered by inflated search spaces attributed to the number of matches that need to be considered due to a lack of enzyme restriction. These large search spaces limit the efficiency with which MHC-I peptides are identified. Here we offer a solution to this problem whereby we describe a targeted database search approach and accompanying tool SpectMHC that is based on a priori predicted MHC-I peptides (Murphy et al., J Proteome Res 16:1806–1816, 2017).Fil: Konda, Prathyusha. Dalhousie University Halifax; CanadáFil: Murphy, J. Patrick. Dalhousie University Halifax; CanadáFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Gujar, Shashi. Dalhousie University Halifax; Canadá. Iwk Health Centre; Canad

Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma

The melanoma genome is dominated by ultraviolet radiation (UVR)-induced mutations. Their relevance in disease progression is unknown. Here we classify melanomas by mutation signatures and identify ten recurrently mutated UVR signature genes that predict patient survival. We validate these findings in primary human melanomas; in mice we show that this signature is imprinted by short-wavelength UVR and that four exposures to UVR are sufficient to accelerate melanomagenesis.This work was supported by CRUK-MI (A27412 and A22902) and the European Research Council (ERC Advanced Grant agreement No. 671262) to R.M. C.G-M. was supported by the French Society of Dermatology, UNICANCER and CEDEF.Peer reviewe

Multiplatform Integrative Analysis of Immunogenomic Data for Biomarker Discovery.

Genomic platforms are increasingly used to gain an understanding of how the immune system responds to cancer. In this chapter we describe steps applied in immunogenomic processing and data processing from multiple genomics platforms to enable study of immune response and the evaluation of candidate biomarkers. We also describe how publicly available web resources can be used to discover and evaluate candidate cancer immune biomarkers