Dataset Information

Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study.

ABSTRACT: Despite the success and fast adaptation of deep learning models in biomedical domains, their lack of interpretability remains an issue. Here, we introduce Enhanced Integrated Gradients (EIG), a method to identify significant features associated with a specific prediction task. Using RNA splicing prediction as well as digit classification as case studies, we demonstrate that EIG improves upon the original Integrated Gradients method and produces sets of informative features. We then apply EIG to identify A1CF as a key regulator of liver-specific alternative splicing, supporting this finding with subsequent analysis of relevant A1CF functional (RNA-seq) and binding data (PAR-CLIP).

SUBMITTER: Jha A

PROVIDER: S-EPMC7305616 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study.

Jha Anupama A K Aicher Joseph J R Gazzara Matthew M Singh Deependra D Barash Yoseph Y

Genome biology 20200619 1

Despite the success and fast adaptation of deep learning models in biomedical domains, their lack of interpretability remains an issue. Here, we introduce Enhanced Integrated Gradients (EIG), a method to identify significant features associated with a specific prediction task. Using RNA splicing prediction as well as digit classification as case studies, we demonstrate that EIG improves upon the original Integrated Gradients method and produces sets of informative features. We then apply EIG to ...[more]

PMID: 32560708

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Project description:Background: Radiofrequency catheter ablation (RFCA) therapy is the first-line treatment for atrial fibrillation (AF), the most common type of cardiac arrhythmia globally. However, the procedure currently has low success rates in dealing with persistent AF, with a reoccurrence rate of ∼50% post-ablation. Therefore, deep learning (DL) has increasingly been applied to improve RFCA treatment for AF. However, for a clinician to trust the prediction of a DL model, its decision process needs to be interpretable and have biomedical relevance. Aim: This study explores interpretability in DL prediction of successful RFCA therapy for AF and evaluates if pro-arrhythmogenic regions in the left atrium (LA) were used in its decision process. Methods: AF and its termination by RFCA have been simulated in MRI-derived 2D LA tissue models with segmented fibrotic regions (n = 187). Three ablation strategies were applied for each LA model: pulmonary vein isolation (PVI), fibrosis-based ablation (FIBRO) and a rotor-based ablation (ROTOR). The DL model was trained to predict the success of each RFCA strategy for each LA model. Three feature attribution (FA) map methods were then used to investigate interpretability of the DL model: GradCAM, Occlusions and LIME. Results: The developed DL model had an AUC (area under the receiver operating characteristic curve) of 0.78 ± 0.04 for predicting the success of the PVI strategy, 0.92 ± 0.02 for FIBRO and 0.77 ± 0.02 for ROTOR. GradCAM had the highest percentage of informative regions in the FA maps (62% for FIBRO and 71% for ROTOR) that coincided with the successful RFCA lesions known from the 2D LA simulations, but unseen by the DL model. Moreover, GradCAM had the smallest coincidence of informative regions of the FA maps with non-arrhythmogenic regions (25% for FIBRO and 27% for ROTOR). Conclusion: The most informative regions of the FA maps coincided with pro-arrhythmogenic regions, suggesting that the DL model leveraged structural features of MRI images to identify such regions and make its prediction. In the future, this technique could provide a clinician with a trustworthy decision support tool.

Dataset Information

Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study.

Publications

Enhanced Integrated Gradients: improving interpretability of deep learning models using splicing codes as a case study.

Similar Datasets

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