biostudies-literatureLou SNational Institute of General Medical SciencesNIGMS NIH HHSe0287521https://www.ebi.ac.uk/biostudies/studies/S-EPMC10793909biostudies-literatureUnknown19(1)The ability to simulate high-throughput data with high fidelity to real experimental data is fundamental for benchmarking methods used to detect true long-range chromatin interactions mediated by a specific protein. Yet, such tools are not currently available. To fill this gap, we develop an in silico experimental procedure, ChIA-Sim, which imitates the experimental procedures that produce real ChIA-PET, Hi-ChIP, or PLAC-seq data. We show the fidelity of ChIA-Sim to real data by using guiding characteristics of several real datasets to generate data using the simulation procedure. We also used ChIA-Sim data to demonstrate the use of our in silico procedure in benchmarking methods for significant interactions analysis by evaluating four methods for significant interaction calling (SIC). In PloS oneAn in silico procedure for generating protein-mediated chromatin interaction data and comparison of significant interaction calling methods.PMC10793909R01 GM114142R01GM114142Lin SLou SfalseAn in silico procedure for generating protein-mediated chromatin interaction data and comparison of significant interaction calling methods.The ability to simulate high-throughput data with high fidelity to real experimental data is fundamental for benchmarking methods used to detect true long-range chromatin interactions mediated by a specific protein. Yet, such tools are not currently available. To fill this gap, we develop an in silico experimental procedure, ChIA-Sim, which imitates the experimental procedures that produce real ChIA-PET, Hi-ChIP, or PLAC-seq data. We show the fidelity of ChIA-Sim to real data by using guiding characteristics of several real datasets to generate data using the simulation procedure. We also used ChIA-Sim data to demonstrate the use of our in silico procedure in benchmarking methods for significant interactions analysis by evaluating four methods for significant interaction calling (SIC). In 2024-01-01T00:00:00Z20242026-05-29T11:21:15.757Z2025-04-06T12:18:43.395ZS-EPMC107939093823210710.1371/journal.pone.0287521