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Abstract

Background:The ever-decreasing cost of Next Generation Sequencing (NGS) has enabled clinical application of genomics in a personalized setting where optimal treatment plans are developed based on a patient’s genetic profile. Especially in cancer, inferences from somatic variants from whole-exome sequencing data have become a key to understanding a patient’s cancer profile for targeted treatment identification regardless of cancer type. The increasing volumes of data necessitate robust and automated pipelines to extract structured information from the detected variants. Although tools and databases exist that partially serve this purpose, they often have disadvantages such as complex command line interfaces, lack of integration as well as standardized input and structured output formats, or data privacy issues when web applications are used to process patient data.
Methods and Results: We introduce Clinical Variant Annotation Pipeline (ClinVAP) that processes, filters, and prioritizes variants in an automated manner. Based on the mutational landscape of the patient, it reveals the mechanisms driving the cancer and lists therapeutics shown to target the genes carrying somatic mutations. By integrating various publicly available databases, we created a comprehensive knowledge base that is used to conduct clinical annotation. ClinVAP is a multistep pipeline consisting of variant annotation, clinical annotation, and report generation steps. The pipeline takes somatic variants in Variant Call Format (VCF) file as input and generates clinical reports in both JSON and DOCX formats (the latter based on user-defined templates) and thus provides the results in both machine and human readable formats. It also ensures reproducibility as it is fully containerized for Docker and Singularity platforms.
Discussion: We provide ClinVAP to create concise and structured clinical reports revealing the important factors in a patient’s tumor profile, which is offered as evidence in targeted therapy selection. As a next step, we plan to conduct a utility assessment together with clinicians to prove ClinVAP’s efficiency and contribution in the clinical decision-making process.