Uncovering Footprints of Natural Selection Through Spectral Analysis of Genomic Summary Statistics.

Natural selection leaves a spatial pattern along the genome, with a haplotype distribution distortion near the selected locus that fades with distance. Evaluating the spatial signal of a population-genetic summary statistic across the genome allows for patterns of natural selection to be distinguished from neutrality. Considering the genomic spatial distribution of multiple summary statistics is expected to aid in uncovering subtle signatures of selection. In recent years, numerous methods have been devised that consider genomic spatial distributions across summary statistics, utilizing both classical machine learning and deep learning architectures. However, better predictions may be attainable by improving the way in which features are extracted from these summary statistics. We apply wavelet transform, multitaper spectral analysis, and S-transform to summary statistic arrays to achieve this goal. Each analysis method converts one-dimensional summary statistic arrays to two-dimensional images of spectral analysis, allowing simultaneous temporal and spectral assessment. We feed these images into convolutional neural networks and consider combining models using ensemble stacking. Our modeling framework achieves high accuracy and power across a diverse set of evolutionary settings, including population size changes and test sets of varying sweep strength, softness, and timing. A scan of central European whole-genome sequences recapitulated well-established sweep candidates and predicted novel cancer-associated genes as sweeps with high support. Given that this modeling framework is also robust to missing genomic segments, we believe that it will represent a welcome addition to the population-genomic toolkit for learning about adaptive processes from genomic data.

Tensor Decomposition-based Feature Extraction and Classification to Detect Natural Selection from Genomic Data.

Inferences of adaptive events are important for learning about traits, such as human digestion of lactose after infancy and the rapid spread of viral variants. Early efforts toward identifying footprints of natural selection from genomic data involved development of summary statistic and likelihood methods. However, such techniques are grounded in simple patterns or theoretical models that limit the complexity of settings they can explore. Due to the renaissance in artificial intelligence, machine learning methods have taken center stage in recent efforts to detect natural selection, with strategies such as convolutional neural networks applied to images of haplotypes. Yet, limitations of such techniques include estimation of large numbers of model parameters under nonconvex settings and feature identification without regard to location within an image. An alternative approach is to use tensor decomposition to extract features from multidimensional data although preserving the latent structure of the data, and to feed these features to machine learning models. Here, we adopt this framework and present a novel approach termed T-REx, which extracts features from images of haplotypes across sampled individuals using tensor decomposition, and then makes predictions from these features using classical machine learning methods. As a proof of concept, we explore the performance of T-REx on simulated neutral and selective sweep scenarios and find that it has high power and accuracy to discriminate sweeps from neutrality, robustness to common technical hurdles, and easy visualization of feature importance. Therefore, T-REx is a powerful addition to the toolkit for detecting adaptive processes from genomic data.

Tensor decomposition based feature extraction and classification to detect natural selection from genomic data.

Inferences of adaptive events are important for learning about traits, such as human digestion of lactose after infancy and the rapid spread of viral variants. Early efforts toward identifying footprints of natural selection from genomic data involved development of summary statistic and likelihood methods. However, such techniques are grounded in simple patterns or theoretical models that limit the complexity of settings they can explore. Due to the renaissance in artificial intelligence, machine learning methods have taken center stage in recent efforts to detect natural selection, with strategies such as convolutional neural networks applied to images of haplotypes. Yet, limitations of such techniques include estimation of large numbers of model parameters under non-convex settings and feature identification without regard to location within an image. An alternative approach is to use tensor decomposition to extract features from multidimensional data while preserving the latent structure of the data, and to feed these features to machine learning models. Here, we adopt this framework and present a novel approach termed T-REx , which extracts features from images of haplotypes across sampled individuals using tensor decomposition, and then makes predictions from these features using classical machine learning methods. As a proof of concept, we explore the performance of T-REx on simulated neutral and selective sweep scenarios and find that it has high power and accuracy to discriminate sweeps from neutrality, robustness to common technical hurdles, and easy visualization of feature importance. Therefore, T-REx is a powerful addition to the toolkit for detecting adaptive processes from genomic data.