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El Mekkaoui, K.

Publications and source records attributed to El Mekkaoui, K..

2 recordsLinked to original sources

Improving Neural Networks for Genotype-Phenotype Prediction Using Published Summary Statistics

Phenotype prediction is a necessity in numerous applications in genetics. However, when the size of the individual-level data of the cohort of interest is small, statistical learning algorithms, from linear regression to neural networks, usually fail due to insufficient data. Fortunately, summary statistics from genome-wide association studies (GWAS) on other large cohorts are often publicly available. In this work, we propose a new regularization method, namely, main effect prior (MEP), for making use of GWAS summary statistics from external datasets. The main effect prior is generally applicable for machine learning algorithms, such as neural networks and linear regression. With simulation and real-world experiments, we show empirically that MEP improves the prediction performance on both homogeneous and heterogeneous datasets. Moreover, deep neural networks with MEP outperform standard baselines even when the training set is small.

bioinformatics↗

Gene-Gene Interaction Detection with Deep Learning

We do not know the extent to which genetic interactions affect the observed phenotype in diseases, because the current interaction detection approaches are limited: they only consider interactions between the top SNPs of each gene, and only simple forms of interaction. We introduce methods for increasing the statistical power of interaction detection by taking into account all SNPs and complex interactions between them, beyond only the currently considered multiplicative relationships. In brief, the relation between SNPs and a phenotype is captured by a gene interaction neural network (NN), and the interactions are quantified by the Shapley score between hidden nodes, which are gene representations that optimally combine information from all SNPs in the gene. Additionally, we design a new permutation procedure tailored for NNs to assess the significance of interactions. The new approach outperformed existing alternatives on simulated datasets, and in a cholesterol study on the UK Biobank it detected six interactions which replicated on an independent FINRISK dataset, four of them novel findings.

bioinformatics↗