Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 57,793 bioRxiv papers from 266,023 authors.
ChromoTrace: Reconstruction of 3D Chromosome Configurations by Super-Resolution Microscopy
Posted 09 Mar 2017
bioRxiv DOI: 10.1101/115436 (published DOI: 10.1371/journal.pcbi.1006002)
Posted 09 Mar 2017
Motivation: The 3D structure of chromatin plays a key role in genome function, in- cluding gene expression, DNA replication, chromosome segregation, and DNA repair. Furthermore the location of genomic loci within the nucleus, especially relative to each other and nuclear structures such as the nuclear envelope and nuclear bodies strongly correlates with aspects of function such as gene expression. Therefore, determining the 3D position of the 6 billion DNA base pairs in each of the 23 chromosomes inside the nucleus of a human cell is a central challenge of biology. Recent advances of super- resolution microscopy in principle enable the mapping of specific molecular features with nanometer precision inside cells. Combined with highly specific, sensitive and multiplexed fluorescence labeling of DNA sequences this opens up the possibility of mapping the 3D path of the genome sequence in situ. Results: Here we develop computational methodologies to reconstruct the sequence configuration of all human chromosomes in the nucleus from a super-resolution image of a set of fluorescent in situ probes hybridized to the genome in a cell. To test our approach we develop a method for the simulation of chromatin packing in an idealized human nucleus. Our reconstruction method, ChromoTrace, uses suffix trees to assign a known linear ordering of in situ probes on the genome to an unknown set of 3D in situ probe positions in the nucleus from super-resolved images using the known genomic probe spacing as a set of physical distance constraints between probes. We find that ChromoTrace can assign the 3D positions of the majority of loci with high accuracy and reasonable sensitivity to specific genome sequences. By simulating spatial resolution, label multiplexing and noise scenarios we assess algorithm performance under realistic experimental constraints. Our study shows that it is feasible to achieve genome-wide reconstruction of the 3D DNA path in chromatin based on super-resolution microscopy images.
- Downloaded 2,356 times
- Download rankings, all-time:
- Site-wide: 1,555 out of 57,793
- In bioinformatics: 312 out of 5,897
- Year to date:
- Site-wide: 22,500 out of 57,793
- Since beginning of last month:
- Site-wide: 33,048 out of 57,793
Downloads over time
Distribution of downloads per paper, site-wide
- Top preprints of 2018
- Paper search
- Author leaderboards
- Overall metrics
- The API
- Email newsletter
- 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!