The identification of cis-regulatory elements: A review from a machine learning perspective.
The majority of the human genome consists of non-coding regions that have been called junk DNA. However, recent studies have unveiled that these regions contain cis-regulatory elements, such as promoters, enhancers, silencers, insulators, etc. These regulatory elements can play crucial roles in controlling gene expressions in specific cell types, conditions, and developmental stages. Disruption to these regions could contribute to phenotype changes. Precisely identifying regulatory elements is key to deciphering the mechanisms underlying transcriptional regulation. Cis-regulatory events are complex processes that involve chromatin accessibility, transcription factor binding, DNA methylation, histone modifications, and the interactions between them. The development of next-generation sequencing techniques has allowed us to capture these genomic features in depth. Applied analysis of genome sequences for clinical genetics has increased the urgency for detecting these regions. However, the complexity of cis-regulatory events and the deluge of sequencing data require accurate and efficient computational approaches, in particular, machine learning techniques. In this review, we describe machine learning approaches for predicting transcription factor binding sites, enhancers, and promoters, primarily driven by next-generation sequencing data. Data sources are provided in order to facilitate testing of novel methods. The purpose of this review is to attract computational experts and data scientists to advance this field.
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia Vancouver, British Columbia V5Z 4H4, Canada; Information and Communications Technologies, National Research Council of Canada, Ottawa, Ontario K1A 0R6, Canada. Electronic address: yifeng.li@nrc-cnrc.gc.ca.
Yifeng
Y
Li
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: juliec@cmmt.ubc.ca.
Chih-Yu
CY
Chen
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: akaye@cmmt.ubc.ca.
Alice M
AM
Kaye
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia Vancouver, British Columbia V5Z 4H4, Canada. Electronic address: wyeth@cmmt.ubc.ca.
Wyeth W
WW
Wasserman
D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods*; D006801:Humans; D000069550:Machine Learning; D008969:Molecular Sequence Data; D010363:Pattern Recognition, Automated / Q000379:methods*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D016415:Sequence Alignment / Q000379:methods; D017422:Sequence Analysis, DNA / Q000379:methods*
Cis-regulatory elements; Data integration; Deep learning; Enhancers; Ensemble learning; Gene regulation; Machine learning; Promoters