fastISM: performant in silico saturation mutagenesis for convolutional neural networks

Bioinformatics. 2022 Apr 28;38(9):2397-2403. doi: 10.1093/bioinformatics/btac135.


Motivation: Deep-learning models, such as convolutional neural networks, are able to accurately map biological sequences to associated functional readouts and properties by learning predictive de novo representations. In silico saturation mutagenesis (ISM) is a popular feature attribution technique for inferring contributions of all characters in an input sequence to the model's predicted output. The main drawback of ISM is its runtime, as it involves multiple forward propagations of all possible mutations of each character in the input sequence through the trained model to predict the effects on the output.

Results: We present fastISM, an algorithm that speeds up ISM by a factor of over 10× for commonly used convolutional neural network architectures. fastISM is based on the observations that the majority of computation in ISM is spent in convolutional layers, and a single mutation only disrupts a limited region of intermediate layers, rendering most computation redundant. fastISM reduces the gap between backpropagation-based feature attribution methods and ISM. It far surpasses the runtime of backpropagation-based methods on multi-output architectures, making it feasible to run ISM on a large number of sequences.

Availability and implementation: An easy-to-use Keras/TensorFlow 2 implementation of fastISM is available at fastISM can be installed using pip install fastism. A hands-on tutorial can be found at

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Mutagenesis
  • Mutation
  • Neural Networks, Computer*