Biology subjects

Giro-i-Nieto, X.

Publications and source records attributed to Giro-i-Nieto, X..

4 recordsLinked to original sources

bioRxiv2023

Deep Variational Autoencoders for Population Genetics

MotivationModern biobanks provide numerous high-resolution genomic sequences of diverse populations. These datasets enable a better understanding of genotype-phenotype interactions with genome-wide association studies (GWAS) and power a new personalized precision medicine with polygenic risk scores (PRS). In order to account for diverse and admixed populations, new algorithmic tools are needed in order to properly capture the genetic composition of populations. Here we explore deep learning techniques, namely variational autoencoders (VAEs), to process genomic data from a population perspective. We hope this work will encourage the adoption of deep neural networks in the population genetics community. ResultsIn this paper, we show the power of VAEs for a variety of tasks relating to the interpretation, classification, simulation, and compression of genomic data with several worldwide whole genome datasets from both humans and canids and evaluate the performance of the proposed applications with and without ancestry conditioning. The unsupervised setting of autoencoders allows for the detection and learning of granular population structure and inferring of informative latent factors. The learned latent spaces of VAEs are able to capture and represent differentiated Gaussian-like clusters of samples with similar genetic composition on a fine-scale from single nucleotide polymorphisms (SNPs), enabling applications in dimensionality reduction, data simulation, and imputation. These individual genotype sequences can then be decomposed into latent representations and reconstruction errors (residuals) which provide a sparse representation useful for lossless compression. We show that different population groups have differentiated compression ratios and classification accuracies. Additionally, we analyze the entropy of the SNP data, its effect on compression across populations, its relation to historical migrations, and we show how to introduce autoencoders into existing compression pipelines.

bioinformatics↗

bioRxiv2022

Predicting Dog Phenotypes from Genotypes

We analyze dog genotypes (i.e., positions of dog DNA sequences that often vary between different dogs) in order to predict the corresponding phenotypes (i.e., unique observed characteristics). More specifically, given chromosome data from a dog, we aim to predict the breed, height, and weight. We explore a variety of linear and non-linear classification and regression techniques to accomplish these three tasks. We also investigate the use of a neural network (both in linear and non-linear modes) for breed classification and compare the performance to traditional statistical methods. We show that linear methods generally outperform or match the performance of non-linear methods for breed classification. However, we show that the reverse is true for height and weight regression. Finally, we evaluate the results of all of these methods based on the number of input features used in the analysis. We conduct experiments using different fractions of the full genomic sequences, resulting in input sequences ranging from 20 SNPs to [~]200k SNPs. In doing so, we explore the impact of using a very limited number of SNPs for prediction. Our experiments demonstrate that these phenotypes in dogs can be predicted with as few as 0.5% of randomly selected SNPs (i.e., 992 SNPs) and that dog breeds can be classified with 50% balanced accuracy with as few as 0.02% SNPs (i.e., 40 SNPs).

genomics↗

bioRxiv2022

Generative Moment Matching Networks for Genotype Simulation

The generation of synthetic genomic sequences using neural networks has potential to ameliorate privacy and data sharing concerns and to mitigate potential bias within datasets due to under-representation of some population groups. However, there is not a consensus on which architectures, training procedures, and evaluation metrics should be used when simulating single nucleotide polymorphism (SNP) sequences with neural networks. In this paper, we explore the use of Generative Moment Matching Networks (GMMNs) for SNP simulation, we present some architectural and procedural changes to properly train the networks, and we introduce an evaluation scheme to qualitatively and quantitatively assess the quality of the simulated sequences.

bioinformatics↗

bioRxiv2021

Neural ADMIXTURE: rapid population clustering with autoencoders

Characterizing the genetic substructure of large cohorts has become increasingly important as genetic association and prediction studies are extended to massive, increasingly diverse, biobanks. ADMIXTURE and STRUCTURE are widely used unsupervised clustering algorithms for characterizing such ancestral genetic structure. These methods decompose individual genomes into fractional cluster assignments with each cluster representing a vector of DNA marker frequencies. The assignments, and clusters, provide an interpretable representation for geneticists to describe population substructure at the sample level. However, with the rapidly increasing size of population biobanks and the growing numbers of variants genotyped (or sequenced) per sample, such traditional methods become computationally intractable. Furthermore, multiple runs with different hyperparameters are required to properly depict the population clustering using these traditional methods, increasing the computational burden. This can lead to days of compute. In this work we present Neural ADMIXTURE, a neural network autoencoder that follows the same modeling assumptions as ADMIXTURE, providing similar (or better) clustering, while reducing the compute time by orders of magnitude. Indeed, the equivalent of one month of continuous compute can be reduced to hours. In addition, Neural ADMIXTURE can include multiple outputs, providing the equivalent results as running the original ADMIXTURE algorithm many times with different numbers of clusters. Our models can also be stored, allowing later cluster assignment to be performed with a linear computational time. The software implementation of Neural ADMIXTURE can be found at https://github.com/ai-sandbox/neural-admixture.

genomics↗