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Correcting gradient-based interpretations of deep neural networks for genomics

Antonio Majdandzic, Chandana Rajesh, Peter K. Koo

2023Genome biology51 citationsDOIOpen Access PDF

Abstract

Post hoc attribution methods can provide insights into the learned patterns from deep neural networks (DNNs) trained on high-throughput functional genomics data. However, in practice, their resultant attribution maps can be challenging to interpret due to spurious importance scores for seemingly arbitrary nucleotides. Here, we identify a previously overlooked attribution noise source that arises from how DNNs handle one-hot encoded DNA. We demonstrate this noise is pervasive across various genomic DNNs and introduce a statistical correction that effectively reduces it, leading to more reliable attribution maps. Our approach represents a promising step towards gaining meaningful insights from DNNs in regulatory genomics.

Topics & Concepts

BiologyGenome BiologyHuman geneticsGenomicsComputational biologyArtificial neural networkEvolutionary biologyComputational genomicsArtificial intelligenceGeneticsGenomeComputer scienceGeneGene expression and cancer classificationMolecular Biology Techniques and ApplicationsGenomics and Phylogenetic Studies