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Feedback GAN for DNA optimizes protein functions

Abstract

Generative adversarial networks (GANs) represent an attractive and novel approach to generate realistic data, such as genes, proteins or drugs, in synthetic biology. Here, we apply GANs to generate synthetic DNA sequences encoding for proteins of variable length. We propose a novel feedback-loop architecture, feedback GAN (FBGAN), to optimize the synthetic gene sequences for desired properties using an external function analyser. The proposed architecture also has the advantage that the analyser does not need to be differentiable. We apply the feedback-loop mechanism to two examples: generating synthetic genes coding for antimicrobial peptides, and optimizing synthetic genes for the secondary structure of their resulting peptides. A suite of metrics, calculated in silico, demonstrates that the GAN-generated proteins have desirable biophysical properties. The FBGAN architecture can also be used to optimize GAN-generated data points for useful properties in domains beyond genomics.

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Fig. 1: FBGAN architecture and training.
Fig. 2: t-SNE visualization of synthetic genes.
Fig. 3: AMP analyser predictions over training epochs.
Fig. 4: Sequence similarity for synthetic AMPs and known AMPs.
Fig. 5: α-helix lengths of known versus synthetic proteins.
Fig. 6: Sample α-helices from FBGAN.

Data availability

Demo, instructions and code for FBGAN are available at https://github.com/av1659/fbgan. All of the data used in this paper are publicly available and can be accessed at the references cited22.

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Acknowledgements

The authors thank A. Kundaje for guidance when initiating the research on GANs and DNA. J.Z. is supported by a Chan-Zuckerberg Biohub Investigator grant and National Science Foundation (NSF) grant CRII 1657155.

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J.Z. conceived the objective of using GANs to generate genes and optimize protein functions; A.G. conceived of and implemented the feedback-loop architecture and conducted the experiments and analysis. Both authors wrote the manuscript.

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Correspondence to James Zou.

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The authors declare no competing interests.

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Gupta, A., Zou, J. Feedback GAN for DNA optimizes protein functions. Nat Mach Intell 1, 105–111 (2019). https://doi.org/10.1038/s42256-019-0017-4

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