EACR25 abstract

doc/Abstracts/2018-06-EACR25.md

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+# 25th Biennial Congress Of The European Association For Cancer Research 2018
+
+## Somatic and germline calls from tumour/normal whole genome data: bioinformatics workflow for reproducible research
+
+
+Szilveszter Juhos 1, 
+Maxime Garcia 2, 
+Teresita Díaz de Ståhl 3, 
+Johanna Sandgren 3, 
+Markus Mayrhofer 4, 
+Max Käller 5, 
+Björn Nystedt 6, 
+Monica Nistér 3
+
+1. Karolinska Institutet, Department of Oncology Pathology, Stockholm, Sweden.
+2. Karolinska Institutet- Science for Life Laboratory, Department of Oncology-Pathology, Stockholm, Sweden.
+3. Karolinska Institutet, Department of Oncology-Pathology, Stockholm, Sweden.
+4. Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
+5. Science for Life Laboratory, Royal Institute of Technology- School of Biotechnology- Division of Gene Technology, Stockholm, Sweden.
+6. Science for Life Laboratory, Department of Cell and Molecular Biology- National Bioinformatics Infrastructure Sweden- Uppsala University, Uppsala, Sweden.
+
+### Introduction
+
+Whole-genome sequencing of cancer tumours is more a research tool nowadays, but going to be used in clinical settings in
+the near future to facilitate precision medicine.  While large institutions have built up in-house bioinformatics
+solutions for their own data analysis, robust and portable workflows combining multiple software have been lacking,
+making it difficult for individual research groups to utilise the potential of this research field. Here we present
+Sarek, a robust, easy-to-install workflow for identification of both somatic and germline mutations from paired
+tumour/normal/relapse samples.
+
+### Material and Methods
+
+Sarek is open source and implemented in Nextflow; a domain specific programming language to enable portability and
+reproducibility. With the help of docker containers the versions of the underlying software can be maintained.
+Furthermore, with Singularity it is possible to run the workflow on protected clusters with no internet connection.
+
+The workflow starts from raw FASTQ files, and follows the GATK best practices to prepare the recalibrated files with
+joint realignment around indels for both the tumour and the normal data. Reads are alignment to the GRCh38 human
+reference in an ALT-aware settings using BWA, however, it is possible to assign other references. HaplotypeCaller and
+Strelka2 germline calls are collected for both the tumour and the normal sample, and Manta provides germline structural
+variants. The somatic variations are calculated by running MuTect2, Strelka and FreeBayes (and MuTect1 optionally).
+Somatic structural variants are delivered by Manta, and ASCAT estimates ploidy, tumour heterogeneity and CNVs.  The
+resulting variant call files are annotated by SnpEff and Ensembl-VEP. The annotated calls are further filtered and
+prioritised by our custom methods. During running the workflow quality control metrics are also calculated and
+aggregated by MultiQC.
+
+### Results and Discussions
+
+Sarek was validated on a real dataset with known golden set of somatic mutations. In a real settings, whole-genome
+sequencing (WGS, 45-60x coverage) of patient-matched tumor and blood derived-DNA is being performed on a set of 80
+pediatric brain tumor samples of the Swedish Childhood Tumor Biobank. The workflow helps to produce, filter, prioritise
+and characterise both germline and somatic variations. 
+
+### Conclusion
+
+Sarek is a portable bioinformatics pipeline for WGS normal/tumour matched samples, aiding precision medicine by improved
+subtyping and to gain novel functional insights in a reproducible framework. 
+
+