Reboot: a straightforward approach to identify genes and splicing isoforms associated with cancer patient prognosis

Autor(es)

dos Santos, Felipe R. C. ; Guardia, Gabriela D. A. ; dos Santos, Filipe F. ; Ohara, Daniel T. ; Galante, Pedro A. F.

• Tipo de documento: Artigo Científico
• Fonte: NAR CANCER; v. 3, n. 2, p. 15-pg., 2021-06-01.

Resumo

Nowadays, the massive amount of data generated by modern sequencing technologies provides an unprecedented opportunity to find genes associated with cancer patient prognosis, connecting basic and translational research. However, treating high dimensionality of gene expression data and integrating it with clinical variables are major challenges to perform these analyses. Here, we present Reboot, an integrative approach to find and validate genes and transcripts (splicing isoforms) associated with cancer patient prognosis from high dimensional expression datasets. Reboot innovates by using amultivariate strategy with penalized Cox regression (LASSO method) combined with a bootstrap approach, in addition to statistical tests and plots to support the findings. Applying Reboot on data from 154 glioblastoma patients, we identified a three-gene signature (IKBIP, OSMR, PODNL1) whose increased derived risk score was significantly associated with worse patients' prognosis. Similarly, Reboot was able to find a seven-splicing isoforms signature related to worse overall survival in 177 pancreatic adenocarcinoma patients with elevated risk scores after uni- and multivariate analyses. In summary, Reboot is an efficient, intuitive and straightforward way of finding genes or splicing isoforms signatures relevant to patient prognosis, which can democratize this kind of analysis and shed light on still under-investigated cancer-related genes and splicing isoforms. (AU)

• Processo FAPESP: 17/18246-7 - Genes colocalizados: estudo de mútua regulação de biogênese entre genes codificadores e não codificadores
• Beneficiário: Felipe Rodolfo Camargo dos Santos
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 18/15579-8 - Retroelementos: uma força motriz criando novidades genéticas no genoma humano e de camundongos
• Beneficiário: Pedro Alexandre Favoretto Galante
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 17/19541-2 - Impacto de proteínas de ligação a RNA na desregulação de splicing em glioblastoma
• Beneficiário: Gabriela Der Agopian Guardia
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/17974-9 - Avaliação de estimativas de heterogeneidade genética intratumoral como marcadores de prognóstico em diferentes tipos de cânceres
• Beneficiário: Filipe Ferreira dos Santos
• Modalidade de apoio: Bolsas no Brasil - Mestrado