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

Author:

dos Santos Felipe R C12,Guardia Gabriela D A1,dos Santos Filipe F13,Ohara Daniel T1,Galante Pedro A F1ORCID

Affiliation:

1. Centro de Oncologia Molecular, Hospital Sirio-Libanes, Sao Paulo, SP 01308-060, Brazil

2. Programa Interunidades em Bioinformatica, Universidade de São Paulo, Sao Paulo, SP 05508-090, Brazil

3. Departamento de Bioquimica, Universidade de Sao Paulo, SP 05508-000, Brazil

Abstract

Abstract 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 a multivariate 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.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo

Instituto Serrapilheira

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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