Banca de DEFESA: LUCAS MARQUES DA CUNHA

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : LUCAS MARQUES DA CUNHA
DATE: 29/11/2022
TIME: 13:30
LOCAL: Google Meet
TITLE:

Development of a computational approach for the analysis and identification of polymorphic peptides

KEY WORDS:

Proteomics. Proteogenomics. Polymorphism. Variant peptides. Custom database. Web Portal.

PAGES: 89
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

The proteomic approach allows large-scale studies of protein expression in different tissues and body fluids, aiming to identify and quantify the total protein content. In the proteomic analysis process, protein identification still presents limitations despite major advances in the area. Frequently, a mass spectrometer is used to generate mass/charge values of the samples. After this process, a reference protein database (eg, UniProt) is usually used to identify proteins. However, using a reference database limits the analysis of the identification of the proteins, since it does not contain the variations in the DNA that can impact the sequence of amino acids, causing incorrect identification or making the process impossible. In this context, there are several custom databases that incorporate such genetic variations. Although they present good results, they are also limited due to the absence of some mutations, becoming another problem in the identification process. A proteogenomics database (dbPepVar) created here combines genetic variation information from dbSNP with protein sequences from NCBI's RefSeq. Public mass spectrometry datasets were used to perform a pan-cancer analysis (Ovarian, Colorectal, Breast, and Prostate), allowing the identification of unique genetic variations. In total 3,726 variant peptides were identified in ovarian cancer samples, 2,543 in prostate, 2,661 in breast and 2,411 in colon-rectal cancer. A mutational frequency analysis showed genes involved in tumor progression processes, sensitivity to chemotherapy, and risk of susceptibility to cancer. Interestingly, in many samples, C-terminal peptides from shortened proteins originating from premature termination codon (PTC) events were identified. This indicates that such proteins had escaped Nonsense-mediated decay (NMD) and, not surprisingly, NMD machinery genes are also mutated in the same samples. This suggests that the vestige of the truncated transcript may be associated with NMD machinery inefficiency caused by gene mutations. In perspective, the web portal developed as well as the analysis performed may direct studies to identify new therapeutic targets for different cancer, and one can also use our database for characterization of variants in samples of unknown genetic background, such as archived samples. The portal is available in: https://bioinfo.imd.ufrn.br/dbPepVar/

COMMITTEE MEMBERS:
Externo à Instituição - FABIO PASSETTI - FIOCRUZ
Externa ao Programa - 1549705 - ADRIANA FERREIRA UCHOA - nullInterno - 1880243 - DANIEL CARLOS FERREIRA LANZA
Presidente - 1267860 - GUSTAVO ANTONIO DE SOUZA
Externo à Instituição - PAULO COSTA CARVALHO - FIOCRUZ