MCI-frcnn: A deep learning method for topological micro-domain boundary detection

Chromatin structural domains, or topologically associated domains (TADs), are a general organizing principle in chromatin biology. RNA polymerase II (RNAPII) mediates multiple chromatin interactive loops, tethering together as RNAPII-associated chromatin interaction domains (RAIDs) to offer a framew...

Full description

Bibliographic Details
Main Authors: Simon Zhongyuan Tian, Pengfei Yin, Kai Jing, Yang Yang, Yewen Xu, Guangyu Huang, Duo Ning, Melissa J. Fullwood, Meizhen Zheng
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-11-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2022.1050769/full
_version_ 1797986674071830528
author Simon Zhongyuan Tian
Pengfei Yin
Kai Jing
Yang Yang
Yewen Xu
Guangyu Huang
Duo Ning
Melissa J. Fullwood
Melissa J. Fullwood
Melissa J. Fullwood
Meizhen Zheng
author_facet Simon Zhongyuan Tian
Pengfei Yin
Kai Jing
Yang Yang
Yewen Xu
Guangyu Huang
Duo Ning
Melissa J. Fullwood
Melissa J. Fullwood
Melissa J. Fullwood
Meizhen Zheng
author_sort Simon Zhongyuan Tian
collection DOAJ
description Chromatin structural domains, or topologically associated domains (TADs), are a general organizing principle in chromatin biology. RNA polymerase II (RNAPII) mediates multiple chromatin interactive loops, tethering together as RNAPII-associated chromatin interaction domains (RAIDs) to offer a framework for gene regulation. RAID and TAD alterations have been found to be associated with diseases. They can be further dissected as micro-domains (micro-TADs and micro-RAIDs) by clustering single-molecule chromatin-interactive complexes from next-generation three-dimensional (3D) genome techniques, such as ChIA-Drop. Currently, there are few tools available for micro-domain boundary identification. In this work, we developed the MCI-frcnn deep learning method to train a Faster Region-based Convolutional Neural Network (Faster R-CNN) for micro-domain boundary detection. At the training phase in MCI-frcnn, 50 images of RAIDs from Drosophila RNAPII ChIA-Drop data, containing 261 micro-RAIDs with ground truth boundaries, were trained for 7 days. Using this well-trained MCI-frcnn, we detected micro-RAID boundaries for the input new images, with a fast speed (5.26 fps), high recognition accuracy (AUROC = 0.85, mAP = 0.69), and high boundary region quantification (genomic IoU = 76%). We further applied MCI-frcnn to detect human micro-TADs boundaries using human GM12878 SPRITE data and obtained a high region quantification score (mean gIoU = 85%). In all, the MCI-frcnn deep learning method which we developed in this work is a general tool for micro-domain boundary detection.
first_indexed 2024-04-11T07:36:53Z
format Article
id doaj.art-dc9b36bedb3f46beb7c5ce9856ed3ac6
institution Directory Open Access Journal
issn 2296-634X
language English
last_indexed 2024-04-11T07:36:53Z
publishDate 2022-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cell and Developmental Biology
spelling doaj.art-dc9b36bedb3f46beb7c5ce9856ed3ac62022-12-22T04:36:43ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-11-011010.3389/fcell.2022.10507691050769MCI-frcnn: A deep learning method for topological micro-domain boundary detectionSimon Zhongyuan Tian0Pengfei Yin1Kai Jing2Yang Yang3Yewen Xu4Guangyu Huang5Duo Ning6Melissa J. Fullwood7Melissa J. Fullwood8Melissa J. Fullwood9Meizhen Zheng10Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaSchool of Biological Sciences, Nanyang Technological University, Singapore, SingaporeCancer Science Institute of Singapore, National University of Singapore, Singapore, SingaporeInstitute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeShenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, ChinaChromatin structural domains, or topologically associated domains (TADs), are a general organizing principle in chromatin biology. RNA polymerase II (RNAPII) mediates multiple chromatin interactive loops, tethering together as RNAPII-associated chromatin interaction domains (RAIDs) to offer a framework for gene regulation. RAID and TAD alterations have been found to be associated with diseases. They can be further dissected as micro-domains (micro-TADs and micro-RAIDs) by clustering single-molecule chromatin-interactive complexes from next-generation three-dimensional (3D) genome techniques, such as ChIA-Drop. Currently, there are few tools available for micro-domain boundary identification. In this work, we developed the MCI-frcnn deep learning method to train a Faster Region-based Convolutional Neural Network (Faster R-CNN) for micro-domain boundary detection. At the training phase in MCI-frcnn, 50 images of RAIDs from Drosophila RNAPII ChIA-Drop data, containing 261 micro-RAIDs with ground truth boundaries, were trained for 7 days. Using this well-trained MCI-frcnn, we detected micro-RAID boundaries for the input new images, with a fast speed (5.26 fps), high recognition accuracy (AUROC = 0.85, mAP = 0.69), and high boundary region quantification (genomic IoU = 76%). We further applied MCI-frcnn to detect human micro-TADs boundaries using human GM12878 SPRITE data and obtained a high region quantification score (mean gIoU = 85%). In all, the MCI-frcnn deep learning method which we developed in this work is a general tool for micro-domain boundary detection.https://www.frontiersin.org/articles/10.3389/fcell.2022.1050769/fulldeep learningtopological micro-domainfaster R-CNN algorithm3D genome organizationdomain boundary
spellingShingle Simon Zhongyuan Tian
Pengfei Yin
Kai Jing
Yang Yang
Yewen Xu
Guangyu Huang
Duo Ning
Melissa J. Fullwood
Melissa J. Fullwood
Melissa J. Fullwood
Meizhen Zheng
MCI-frcnn: A deep learning method for topological micro-domain boundary detection
Frontiers in Cell and Developmental Biology
deep learning
topological micro-domain
faster R-CNN algorithm
3D genome organization
domain boundary
title MCI-frcnn: A deep learning method for topological micro-domain boundary detection
title_full MCI-frcnn: A deep learning method for topological micro-domain boundary detection
title_fullStr MCI-frcnn: A deep learning method for topological micro-domain boundary detection
title_full_unstemmed MCI-frcnn: A deep learning method for topological micro-domain boundary detection
title_short MCI-frcnn: A deep learning method for topological micro-domain boundary detection
title_sort mci frcnn a deep learning method for topological micro domain boundary detection
topic deep learning
topological micro-domain
faster R-CNN algorithm
3D genome organization
domain boundary
url https://www.frontiersin.org/articles/10.3389/fcell.2022.1050769/full
work_keys_str_mv AT simonzhongyuantian mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT pengfeiyin mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT kaijing mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT yangyang mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT yewenxu mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT guangyuhuang mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT duoning mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT melissajfullwood mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT melissajfullwood mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT melissajfullwood mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection
AT meizhenzheng mcifrcnnadeeplearningmethodfortopologicalmicrodomainboundarydetection