Using FunSeq2 for Coding and Non‐Coding Variant Annotation and Prioritization

Priyanka Dhingra1, Yao Fu2, Mark Gerstein3, Ekta Khurana4

1 Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York 10021, 2 Bina Technologies, Roche Sequencing, Redwood City, California, 3 Department of Computer Science, Yale University, New Haven, Connecticut, 4 Englander Institute for Precision Medicine, Weill Cornell Medical College, New York, New York
Publication Name:  Current Protocols in Bioinformatics
Unit Number:  Unit 15.11
DOI:  10.1002/cpbi.23
Online Posting Date:  May, 2017
GO TO THE FULL TEXT: PDF or HTML at Wiley Online Library

Abstract

The identification of non‐coding drivers remains a challenge and bottleneck for the use of whole‐genome sequencing in the clinic. FunSeq2 is a computational tool for annotation and prioritization of somatic mutations in coding and non‐coding regions. It integrates a data context made from large‐scale genomic datasets and uses a high‐throughput variant prioritization pipeline. This unit provides guidelines for installing and running FunSeq2 to (a) annotate and prioritize variants, (b) incorporate user‐defined annotations, and (c) detect differential gene expression. © 2017 by John Wiley & Sons, Inc.

Keywords: disease‐causing; differential gene expression; cancer drivers; indels; non‐coding variants; single nucleotide variants

     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Table of Contents

  • Introduction
  • Basic Protocol 1: Using FunSeq2 Variant Annotation and Prioritization Via the Web Interface
  • Basic Protocol 2: Using the Command‐Line LINUX/MAC OS Compatible Version of FunSeq2 for Variant Annotation and Prioritization
  • Basic Protocol 3: FunSeq2 for Detection of Differentially Expressed Genes
  • Support Protocol 1: Running FunSeq2 with User Data Context
  • Guidelines for Understanding Results
  • Commentary
  • Literature Cited
  • Figures
  • Tables
     
 
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Materials

GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library

Figures

Videos

Literature Cited

Literature Cited
  Dunham, I. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57–74. doi: 10.1038/nature11247
  Fu, Y., Liu, Z., Lou, S., Bedford, J., Mu, X. J., Yip, K. Y., … Gerstein, M. (2014). FunSeq2: A framework for prioritizing noncoding regulatory variants in cancer. Genome biology, 15, 480. doi: 10.1186/s13059‐014‐0480‐5
  Habegger, L., Balasubramanian, S., Chen, D. Z., Khurana, E., Sboner, A., Harmanci, A., … Gerstein, M. (2012). VAT: A computational framework to functionally annotate variants in personal genomes within a cloud‐computing environment. Bioinformatics, 28, 2267–2269. doi: 10.1093/bioinformatics/bts368
  Huang, F. W., Hodis, E., Xu, M. J., Kryukov, G. V., Chin, L., & Garraway, L. A. (2013). Highly recurrent TERT promoter mutations in human melanoma. Science, 339, 957–959. doi: 10.1126/science.1229259
  Khurana, E., Fu, Y., Chakravarty, D., Demichelis, F., Rubin, M. A., & Gerstein, M. (2016). Role of non‐coding sequence variants in cancer. Nature Reviews Genetics, 17, 93–108. doi: 10.1038/nrg.2015.17
  Khurana, E., Fu, Y., Colonna, V., Mu, X. J., Kang, H. M., Lappalainen, T., … Gerstein, M. (2013). Integrative annotation of variants from 1092 humans: Application to cancer genomics. Science, 342, 1235587. doi: 10.1126/science.1235587
  Mardis, E. R., & Wilson, R. K. (2009). Cancer genome sequencing: A review. Human Molecular Genetics, 18, R163–168. doi: 10.1093/hmg/ddp396
  Pon, J. R., & Marra, M. A. (2015). Driver and passenger mutations in cancer. Annual Review of Pathology, 10, 25–50. doi: 10.1146/annurev‐pathol‐012414‐040312
  Quinlan, A. R. (2014). BEDTools: The Swiss‐Army Tool for Genome Feature Analysis. Current Protocols in Bioinformatics, 47, 11.12.1–11.12.34.
  Roadmap Epigenomics, C., Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., … Kellis, M. (2015). Integrative analysis of 111 reference human epigenomes. Nature, 518, 317–330. doi: 10.1038/nature14248
  Ward, L. D., & Kellis, M. 2012. Interpreting noncoding genetic variation in complex traits and human disease. Nature Biotechnology, 30, 1095–1106. doi: 10.1038/nbt.2422
  Yip, K. Y., Cheng, C., Bhardwaj, N., Brown, J. B., Leng, J., Kundaje, A., … Gerstein, M. 2012. Classification of human genomic regions based on experimentally determined binding sites of more than 100 transcription‐related factors. Genome Biology, 13, R48. doi: 10.1186/gb‐2012‐13‐9‐r48
GO TO THE FULL PROTOCOL:
PDF or HTML at Wiley Online Library