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Machine Learning based histology phenotyping to investigate the epidemiologic and genetic basis of adipocyte morphology and cardiometabolic traits.

Authors :
Craig A Glastonbury
Sara L Pulit
Julius Honecker
Jenny C Censin
Samantha Laber
Hanieh Yaghootkar
Nilufer Rahmioglu
Emilie Pastel
Katerina Kos
Andrew Pitt
Michelle Hudson
Christoffer Nellåker
Nicola L Beer
Hans Hauner
Christian M Becker
Krina T Zondervan
Timothy M Frayling
Melina Claussnitzer
Cecilia M Lindgren
Source :
PLoS Computational Biology, Vol 16, Iss 8, p e1008044 (2020)
Publication Year :
2020
Publisher :
Public Library of Science (PLoS), 2020.

Abstract

Genetic studies have recently highlighted the importance of fat distribution, as well as overall adiposity, in the pathogenesis of obesity-associated diseases. Using a large study (n = 1,288) from 4 independent cohorts, we aimed to investigate the relationship between mean adipocyte area and obesity-related traits, and identify genetic factors associated with adipocyte cell size. To perform the first large-scale study of automatic adipocyte phenotyping using both histological and genetic data, we developed a deep learning-based method, the Adipocyte U-Net, to rapidly derive mean adipocyte area estimates from histology images. We validate our method using three state-of-the-art approaches; CellProfiler, Adiposoft and floating adipocytes fractions, all run blindly on two external cohorts. We observe high concordance between our method and the state-of-the-art approaches (Adipocyte U-net vs. CellProfiler: R2visceral = 0.94, P < 2.2 × 10-16, R2subcutaneous = 0.91, P < 2.2 × 10-16), and faster run times (10,000 images: 6mins vs 3.5hrs). We applied the Adipocyte U-Net to 4 cohorts with histology, genetic, and phenotypic data (total N = 820). After meta-analysis, we found that mean adipocyte area positively correlated with body mass index (BMI) (Psubq = 8.13 × 10-69, βsubq = 0.45; Pvisc = 2.5 × 10-55, βvisc = 0.49; average R2 across cohorts = 0.49) and that adipocytes in subcutaneous depots are larger than their visceral counterparts (Pmeta = 9.8 × 10-7). Lastly, we performed the largest GWAS and subsequent meta-analysis of mean adipocyte area and intra-individual adipocyte variation (N = 820). Despite having twice the number of samples than any similar study, we found no genome-wide significant associations, suggesting that larger sample sizes and a homogenous collection of adipose tissue are likely needed to identify robust genetic associations.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
1553734X and 15537358
Volume :
16
Issue :
8
Database :
Directory of Open Access Journals
Journal :
PLoS Computational Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.9574c1c2a4be88137af51b58a2170
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pcbi.1008044