15P - ClinBioNGS: An integrated clinical bioinformatics pipeline for the analysis of somatic NGS cancer panels

Background

Tumor targeted sequencing panels currently in use cover both DNA and RNA alterations in order to improve the molecular clinical diagnostics process. However, in terms of bioinformatics analysis, commercial panels often provide proprietary and non-customizable solutions which cannot be tailored to the user preferences. Additionally, these tools offer very limited graphical reports, hindering the interpretability of the results. Here we present ClinBioNGS, an open-source and customizable clinical bioinformatics pipeline to identify both DNA and RNA alterations in targeted NGS panels. ClinBioNGS provides interpretable and visual results, and can also keep an up-to-date database of all identified alterations in the samples sequenced in the laboratory. ClinBioNGS currently works both for Illumina TruSight Oncology 500 (TSO 500) and ThermoFisher Oncomine Precision (OPA) and Comprehensive (OCA) panels.

Methods

ClinBioNGS can detect small variants (SNVs and InDels), copy number alterations (CNAs), cancer-related splice variants, and gene fusions. Our tool also performs extensive coverage analyses, and calculates tumor mutational burden (TMB) and microsatellite instability (MSI) for panels covering these features. It is implemented in Bash script, R/Shiny for reporting and plots, and SQLite as the back-end database.

Results

We have compared the results of our pipeline to the commercial one in 500 samples profiled in-house with Illumina TSO 500. ClinBioNGS detected more than 99% of all the alterations reported by Illumina. Additionally, we reported 7% more pathogenic SNVs/InDels and ∼4X more cancer-related CNAs. We also detected 31% more cancer-related fusions (66 vs 87), with 7 of them being potentially actionable (e.g. NTRK1, MET, BRAF fusions). Both pipelines detect the same number of splice variants (32), but we also identified a large set (5578) of cancer-related splice alterations that TSO500 failed to report. A similar analysis with samples profiled with ThermoFisher OPA is currently ongoing.

Conclusions

We present ClinBioNGS, a complete bioinformatics pipeline that allows for a better detection, visualization and interpretation of tumor alterations in the context of somatic molecular diagnostics of cancer patients.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Ministerio de Universidades (FPU Grant).

Disclosure

X. Sole: Financial Interests, Personal, Invited Speaker: Roche. V. Moreno Aguado: Financial Interests, Personal, Stocks/Shares, Biotech company: Aniling. E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Lilly, Janssen, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Boehringer Ingelheim, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Funding, Merck-Serono funded a clinical trial: Merck-Serono; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche. All other authors have declared no conflicts of interest.