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Semantically Rich Local Dataset Generation for Explainable AI in Genomics

Published: 14 July 2024 Publication History

Abstract

Black box deep learning models trained on genomic sequences excel at predicting the outcomes of different gene regulatory mechanisms. Therefore, interpreting these models may provide novel insights into the underlying biology, supporting downstream biomedical applications. Due to their complexity, interpretable surrogate models can only be built for local explanations (e.g., a single instance). However, accomplishing this requires generating a dataset in the neighborhood of the input, which must maintain syntactic similarity to the original data while introducing semantic variability in the model's predictions. This task is challenging due to the complex sequence-to-function relationship of DNA.
We propose using Genetic Programming to generate datasets by evolving perturbations in sequences that contribute to their semantic diversity. Our custom, domain-guided individual representation effectively constrains syntactic similarity, and we provide two alternative fitness functions that promote diversity with no computational effort. Applied to the RNA splicing domain, our approach quickly achieves good diversity and significantly outperforms a random baseline in exploring the search space, as shown by our proof-of-concept, short RNA sequence. Furthermore, we assess its generalizability and demonstrate scalability to larger sequences, resulting in a ≈30% improvement over the baseline.

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    cover image ACM Conferences
    GECCO '24: Proceedings of the Genetic and Evolutionary Computation Conference
    July 2024
    1657 pages
    ISBN:9798400704949
    DOI:10.1145/3638529
    This work is licensed under a Creative Commons Attribution International 4.0 License.

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    Published: 14 July 2024

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    Author Tags

    1. evolutionary computation
    2. instance generation
    3. combinatorial optimization
    4. local explainability
    5. RNA splicing

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    GECCO '24: Genetic and Evolutionary Computation Conference
    July 14 - 18, 2024
    VIC, Melbourne, Australia

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