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Background: Genetic variation provides a foundation for understanding evolution. With the rise of artificial intelligence, machine learning has emerged as a powerful tool for identifying genomic footprints of evolutionary processes through simulation-based predictive modeling. However, existing approaches require prior knowledge of the factors shaping genetic variation, whereas uncovering anomalous genomic regions regardless of their causes remains an equally important and complementary endeavor. Methods: To address this problem, we introduce ANDES (ANomaly DEtection using Summary statistics), a suite of algorithms that apply statistical techniques to extract features for unsupervised anomaly detection. A key innovation of ANDES is its ability to account for autocovariation due to linkage disequilibrium by fitting curves to contiguous windows and computing their first and second derivatives, thereby capturing the “velocity” and “acceleration” of genetic variation. These features are then used to train models that flag biologically significant or artifactual regions. Results: Application to human genomic data demonstrates that ANDES successfully detects anomalous regions that colocalize with genes under positive or balancing selection. Moreover, these analyses reveal a non-uniform distribution of anomalies, which are enriched in specific autosomes, intergenic regions, introns, and regions with low GC content, repetitive sequences, and poor mappability. Conclusions: ANDES thus offers a novel, model-agnostic framework for uncovering anomalous genomic regions in both model and non-model organisms.