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

Author(s)

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

• Document type: Journal article
• Source: NAR CANCER; v. 3, n. 2, p. 15-pg., 2021-06-01.

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 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)

• FAPESP's process: 17/18246-7 - Overlapped genes: mutual regulation of coding and noncoding genes biogenesis
• Grantee: Felipe Rodolfo Camargo dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 18/15579-8 - Retroelements: a driving force generating genetic novelties in the human and mouse genome
• Grantee: Pedro Alexandre Favoretto Galante
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 17/19541-2 - Impact of RNA binding proteins on abnormal regulation of splicing in glioblastoma
• Grantee: Gabriela Der Agopian Guardia
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/17974-9 - Assessment of intratumoral genetic heterogeneity estimates as prognostic markers across several cancer types
• Grantee: Filipe Ferreira dos Santos
• Support Opportunities: Scholarships in Brazil - Master