The Advanced Biomedical Computational Sciences group within FNL's Bioinformatics and Computational Science Directorate provides bioinformatics assistance in designing, analyzing, and interpreting high throughput biological experiments. Support spans many aspects of genomics including variation profiling, understanding basic biology, identifying biological markers causative or associated with disease, as well as identifying potential therapeutic leads. The case study showcases one of our recent efforts on comprehensive NGS analysis and data management support. 

The NCI CLARITY (Cancers of the Liver: Accelerating Research of Immunotherapy by a TransdisciplinarY Network) project is a multi-institutional and multidisciplinary study involving collaboration between NCI and several domestic clinical institutions. The Accelerating Biomedical Computational Science group provided comprehensive bioinformatic support and data management.  

The group did this work for the retrospective arm of the study that used archived formalin-fixed, paraffin-embedded samples to profile the transcriptome and genomic alterations among 86 hepatocellular carcinoma and biliary tract cancer patients prior to and following immune checkpoint inhibitor treatment.  

Using supervised and unsupervised approaches, the study identified and distinguished stable molecular subtypes linked to overall survival by two axes of aggressive tumor biology and microenvironmental features. Moreover, as molecular responses to immune checkpoint inhibitor treatment differed between subtypes, the study highlighted that patients with heterogeneous liver cancer may be stratified by molecular status indicative of treatment response to immune checkpoint inhibitors. ABCS team member Erica Pehrsson is a co-first author on a publication that resulted from this effort

Our contributions

  • Assembled patient and sample metadata from sources including external study sites, the Laboratory of Pathology, Molecular Histology Laboratory, and the Sequencing Facility, which informed selection of the final sample set. 

  • Uniformly processed 296 RNAseq samples using CCBR-Pipeliner on the Biowulf HPC. 

  • Performed QC and downstream analysis of RNAseq and WES samples, including consensus clustering, survival analysis, immune infiltration, gene set enrichment analysis, and mutation signature analysis. 

  • Performed an extensive comparison of matched formalin-fixed paraffin embedded (FFPE) and frozen samples to determine the extent of technical artefacts. 

  • Coordinated data across multiple systems (CDSP, LabMatrix, HALO, and NIDAP), including building novel tools to automatically validate submitted clinical data, transfer data, and build reports. 

  • Interfaced with primary investigators, clinicians, and laboratory members, external sites, data managers, research nurses, core staff, and contracts.