title: HiC-bench: comprehensive and reproducible Hi-C data analysis designed for parameter exploration and benchmarking.
abstract: Chromatin conformation capture techniques have evolved rapidly over the last few years and have provided new insights into genome organization at an unprecedented resolution. Analysis of Hi-C data is complex and computationally intensive involving multiple tasks and requiring robust quality assessment. This has led to the development of several tools and methods for processing Hi-C data. However, most of the existing tools do not cover all aspects of the analysis and only offer few quality assessment options. Additionally, availability of a multitude of tools makes scientists wonder how these tools and associated parameters can be optimally used, and how potential discrepancies can be interpreted and resolved. Most importantly, investigators need to be ensured that slight changes in parameters and/or methods do not affect the conclusions of their studies.
  
  
  
  To address these issues (compare, explore and reproduce), we introduce HiC-bench, a configurable computational platform for comprehensive and reproducible analysis of Hi-C sequencing data. HiC-bench performs all common Hi-C analysis tasks, such as alignment, filtering, contact matrix generation and normalization, identification of topological domains, scoring and annotation of specific interactions using both published tools and our own. We have also embedded various tasks that perform quality assessment and visualization. HiC-bench is implemented as a data flow platform with an emphasis on analysis reproducibility. Additionally, the user can readily perform parameter exploration and comparison of different tools in a combinatorial manner that takes into account all desired parameter settings in each pipeline task. This unique feature facilitates the design and execution of complex benchmark studies that may involve combinations of multiple tool/parameter choices in each step of the analysis. To demonstrate the usefulness of our platform, we performed a comprehensive benchmark of existing and new TAD callers exploring different matrix correction methods, parameter settings and sequencing depths. Users can extend our pipeline by adding more tools as they become available.
  
  
  
  HiC-bench consists an easy-to-use and extensible platform for comprehensive analysis of Hi-C datasets. We expect that it will facilitate current analyses and help scientists formulate and test new hypotheses in the field of three-dimensional genome organization.
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA.|Laura and Isaac Perlmutter Cancer Center and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, 10016, USA.
authors.forename: Charalampos
authors.initials: C
authors.lastname: Lazaris
authors.affiliation: Applied Bioinformatics Laboratories, Office of Science & Research, NYU School of Medicine, New York, NY, 10016, USA.|Genome Technology Center, Office of Science & Research, NYU School of Medicine, New York, NY, 10016, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Ntziachristos
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA. ioannis.aifantis@nyumc.org.|Laura and Isaac Perlmutter Cancer Center and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, 10016, USA. ioannis.aifantis@nyumc.org.
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY, 10016, USA. aristotelis.tsirigos@nyumc.org.|Laura and Isaac Perlmutter Cancer Center and Helen L. and Martin S. Kimmel Center for Stem Cell Biology, NYU School of Medicine, New York, NY, 10016, USA. aristotelis.tsirigos@nyumc.org.|Applied Bioinformatics Laboratories, Office of Science & Research, NYU School of Medicine, New York, NY, 10016, USA. aristotelis.tsirigos@nyumc.org.|Genome Technology Center, Office of Science & Research, NYU School of Medicine, New York, NY, 10016, USA. aristotelis.tsirigos@nyumc.org.
authors.forename: Aristotelis
authors.identifier: 0000-0002-7512-8477
authors.initials: A
authors.lastname: Tsirigos
mesh_terms: D000465:Algorithms; D002843:Chromatin / Q000235:genetics*; D019295:Computational Biology / Q000379:methods / Q000592:standards; D030561:Databases, Nucleic Acid; D023281:Genomics / Q000379:methods* / Q000592:standards; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D058977:Molecular Sequence Annotation; D015203:Reproducibility of Results; D012984:Software; D057188:Workflow
chemical_list: D002843:Chromatin
keywords: Benchmarking; Chromosome conformation; Computational pipeline; Data provenance; Hi-C; Parameter exploration