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Machine Learning based histology phenotyping to investigate the epidemiologic and genetic basis of adipocyte morphology and cardiometabolic traits
- Source :
- PLoS Computational Biology, Vol 16, Iss 8, p e1008044 (2020), PLoS Computational Biology
- 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.<br />Author summary Fundamental aspects of biology such as how the size or number of adipocytes relates to obesity and cardiometabolic health are still unanswered. To answer such questions, fast, accurate and automated measurements need to be acquired, free from human biases. Glastonbury et al., 2020 describe a novel machine learning method to perform rapid acquisition of adipocyte area estimates from histological imaging data. Using these imaging derived phenotypes, Glastonbury et al., 2020 assess the relationship between adipocyte size and a range of cardio-metabolic comorbidities, demonstrating that adipocyte size can vary depending on where adipose is stored throughout the body. By tying genetics with imaging data, Glastonbury et al., 2020 were able to demonstrate that previous findings associating adipocyte size with Type 2 Diabetes variants, are likely to be false positives. This study provides a means of being able to scale up GWAS type analyses to imaging derived phenotypes.
- Subjects :
- 0301 basic medicine
Male
Physiology
Single Nucleotide Polymorphisms
Adipose tissue
Genome-wide association study
Body Mass Index
Machine Learning
chemistry.chemical_compound
0302 clinical medicine
Mathematical and Statistical Techniques
Polymorphism (computer science)
Animal Cells
Adipocyte
Adipocytes
Medicine and Health Sciences
Biology (General)
Connective Tissue Cells
Ecology
Statistics
Genomics
Metaanalysis
Middle Aged
Phenotypes
Phenotype
Computational Theory and Mathematics
Adipose Tissue
Physiological Parameters
Connective Tissue
Modeling and Simulation
Physical Sciences
Female
Anatomy
Cellular Types
Research Article
Adult
medicine.medical_specialty
Histology
QH301-705.5
Single-nucleotide polymorphism
Biology
Research and Analysis Methods
Polymorphism, Single Nucleotide
03 medical and health sciences
Cellular and Molecular Neuroscience
Internal medicine
medicine
Genome-Wide Association Studies
Genetics
Humans
Obesity
Statistical Methods
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Cell Size
Body Weight
Biology and Life Sciences
Computational Biology
Human Genetics
Cell Biology
medicine.disease
Genome Analysis
030104 developmental biology
Endocrinology
Biological Tissue
chemistry
Sample size determination
Neural Networks, Computer
Body mass index
030217 neurology & neurosurgery
Mathematics
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 16
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....11be69b3abf6ccaa38bd1cbab9eab888