TY - JOUR

T1 - Transfer learning identifies sequence determinants of cell-type specific regulatory element accessibility

AU - Salvatore, Marco

AU - Horlacher, Marc

AU - Marsico, Annalisa

AU - Winther, Ole

AU - Andersson, Robin

PY - 2023

Y1 - 2023

N2 - Dysfunction of regulatory elements through genetic variants is a central mechanism in the pathogenesis of disease. To better understand disease etiology, there is consequently a need to understand how DNA encodes regulatory activity. Deep learning methods show great promise for modeling of biomolecular data from DNA sequence but are limited to large input data for training. Here, we develop ChromTransfer, a transfer learning method that uses a pre-trained, cell-type agnostic model of open chromatin regions as a basis for fine-tuning on regulatory sequences. We demonstrate superior performances with ChromTransfer for learning cell-type specific chromatin accessibility from sequence compared to models not informed by a pre-trained model. Importantly, ChromTransfer enables fine-tuning on small input data with minimal decrease in accuracy. We show that ChromTransfer uses sequence features matching binding site sequences of key transcription factors for prediction. Together, these results demonstrate ChromTransfer as a promising tool for learning the regulatory code.

AB - Dysfunction of regulatory elements through genetic variants is a central mechanism in the pathogenesis of disease. To better understand disease etiology, there is consequently a need to understand how DNA encodes regulatory activity. Deep learning methods show great promise for modeling of biomolecular data from DNA sequence but are limited to large input data for training. Here, we develop ChromTransfer, a transfer learning method that uses a pre-trained, cell-type agnostic model of open chromatin regions as a basis for fine-tuning on regulatory sequences. We demonstrate superior performances with ChromTransfer for learning cell-type specific chromatin accessibility from sequence compared to models not informed by a pre-trained model. Importantly, ChromTransfer enables fine-tuning on small input data with minimal decrease in accuracy. We show that ChromTransfer uses sequence features matching binding site sequences of key transcription factors for prediction. Together, these results demonstrate ChromTransfer as a promising tool for learning the regulatory code.

KW - TRANSCRIPTION FACTORS

KW - GENE-EXPRESSION

KW - ENHANCERS

KW - BINDING

KW - GENOME

U2 - 10.1093/nargab/lqad026

DO - 10.1093/nargab/lqad026

M3 - Journal article

C2 - 37007588

VL - 5

JO - NAR Genomics and Bioinformatics

JF - NAR Genomics and Bioinformatics

SN - 2631-9268

IS - 2

M1 - 026

ER -