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Record W3214319465 · doi:10.1101/2021.11.15.468756

cSurvival: a web resource for biomarker interactions in cancer outcomes

2021· preprint· en· W3214319465 on OpenAlexafffund
Xuanjin Cheng, Yongxing Liu, Jiahe Wang, Yujie Chen, A. Gordon Robertson, Xuekui Zhang, Steven J.M. Jones, Stefan Taubert

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2021
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsUniversity of VictoriaCanada's Michael Smith Genome Sciences CentreBC Children's HospitalUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaChinese University of Hong KongCanada Research ChairsSimon Fraser UniversityUniversity of British ColumbiaCanadian Institutes of Health ResearchCanada's Michael Smith Genome Sciences Centre
KeywordsBiomarkerCancerColorectal cancerComputational biologyBioinformaticsOncologyBiologyMedicineInternal medicineGenetics

Abstract

fetched live from OpenAlex

ABSTRACT Survival analysis is a technique to identify prognostic biomarkers and genetic vulnerabilities in cancer studies. Large-scale consortium-based projects have profiled >11,000 adult and >4,000 paediatric tumor cases with clinical outcomes and multi-omics approaches. This provides a resource for investigating molecular-level cancer etiologies using clinical correlations. Although cancers often arise from multiple genetic vulnerabilities and have deregulated gene sets (GSs), existing survival analysis protocols can report only on individual genes. Additionally, there is no systematic method to connect clinical outcomes with experimental (cell line) data. To address these gaps, we developed cSurvival ( https://tau.cmmt.ubc.ca/cSurvival ). cSurvival provides a user-adjustable analytical pipeline with a curated, integrated database, and offers three main advances: (a) joint analysis with two genomic predictors to identify interacting biomarkers, including new algorithms to identify optimal cutoffs for two continuous predictors; (b) survival analysis not only at the gene, but also the GS level; and (c) integration of clinical and experimental cell line studies to generate synergistic biological insights. To demonstrate these advances, we report three case studies. We confirmed findings of autophagy-dependent survival in colorectal cancers and of synergistic negative effects between high expression of SLC7A11 and SLC2A1 on outcomes in several cancers. We further used cSurvival to identify high expression of the Nrf2-antioxidant response element pathway as a main indicator for lung cancer prognosis and for cellular resistance to oxidative stress-inducing drugs. Together, these analyses demonstrate cSurvival’s ability to support biomarker prognosis and interaction analysis via gene- and GS-level approaches and to integrate clinical and experimental biomedical studies. Key points We developed cSurvival, an advanced framework using clinical correlations to study biomarker interactions in cancers, with source code and curated datasets freely available for all cSurvival includes new algorithms to identify optimal cutoffs for two continuous predictors to stratify patients into risk groups, enabling for the first time joint analysis with two genomic predictors; cSurvival allows survival analysis at the gene set (GS) level with comprehensive and up-to-date GS libraries The cSurvival pipeline integrates clinical outcomes and experimental cancer cell line data to generate synergistic biological insights and to mine for appropriate preclinical cell line tools cSurvival is built on a manually curated cancer outcomes database

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.002
metaresearch head score (Gemma)0.010
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: Not applicable
GenreCandidate signal: Software · Consensus signal: none
Teacher disagreement score0.063
Threshold uncertainty score0.210

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0020.010
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0020.002
Bibliometrics0.0080.006
Science and technology studies0.0010.000
Scholarly communication0.0030.002
Open science0.0030.005
Research integrity0.0010.002
Insufficient payload (model declined to judge)0.0630.028

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.031
GPT teacher head0.295
Teacher spread0.264 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreSoftware

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2021
Admission routes2
Has abstractyes

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