Chromosome-Conformation-Capture-Carbon-Copy (5C) is a molecular technology based on proximity ligation that enables high-resolution and high coverage inquiry of long-range chromatin looping interactions. Computational pipelines for analyzing 5C data involve a series of inter-dependent normalization procedures and statistical methods that markedly influence downstream biological results. A detailed analysis of the trade-offs inherent to all stages of 5C analysis has not been reported, but is essential for understanding the biological basis of looping. Here, we provide a comparative assessment of method performance at each step in the 5C analysis pipeline, including sequencing depth and library complexity correction, bias mitigation, spatial noise reduction, distance-dependent expected and variance estimation, modeling, and loop detection. We present a detailed discussion of methodological advantages/disadvantages at each step and provide a full suite of algorithms, lib5C, to allow investigators to test the range of approaches on their own high-resolution 5C data. Principles learned from our comparative analyses will have broad impact on many other forms of Chromosome-Conformation-Capture-based data, including Hi-C, 4C, and Capture-C.
- Downloaded 500 times
- Download rankings, all-time:
- Site-wide: 37,677 out of 103,764
- In genomics: 3,571 out of 6,382
- Year to date:
- Site-wide: 94,757 out of 103,764
- Since beginning of last month:
- Site-wide: 97,116 out of 103,764
Downloads over time
Distribution of downloads per paper, site-wide
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!