ProteInfer, deep neural networks for protein functional inference

  1. Theo Sanderson  Is a corresponding author
  2. Maxwell L Bileschi
  3. David Belanger
  4. Lucy J Colwell
  1. The Francis Crick Institute, United Kingdom
  2. Google AI, United States

Abstract

Predicting the function of a protein from its amino acid sequence is a long-standing challenge in bioinformatics. Traditional approaches use sequence alignment to compare a query sequence either to thousands of models of protein families or to large databases of individual protein sequences. Here we introduce ProteInfer, which instead employs deep convolutional neural networks to directly predict a variety of protein functions - EC numbers and GO terms - directly from an unaligned amino acid sequence. This approach provides precise predictions which complement alignment-based methods, and the computational efficiency of a single neural network permits novel and lightweight software interfaces, which we demonstrate with an in-browser graphical interface for protein function prediction in which all computation is performed on the user's personal computer with no data uploaded to remote servers. Moreover, these models place full-length amino acid sequences into a generalised functional space, facilitating downstream analysis and interpretation. To read the interactive version of this paper, please visit https://google-research.github.io/proteinfer/.

Data availability

Source code is available on GitHub from https://github.com/google-research/proteinfer. Processed TensorFlow files are available from the indicated URLs. Raw training data is from UniProt.

The following previously published data sets were used

Article and author information

Author details

  1. Theo Sanderson

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    theo.sanderson@crick.ac.uk
    Competing interests
    Theo Sanderson, performed research as part of their employment at Google LLC. Google is a technology company that sells machine learning services as part of its business. Portions of this work are covered by US patent WO2020210591A1, filed by Google..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4177-2851
  2. Maxwell L Bileschi

    Google AI, Boston, United States
    Competing interests
    Maxwell L Bileschi, performed research as part of their employment at Google LLC. Google is a technology company that sells machine learning services as part of its business. Portions of this work are covered by US patent WO2020210591A1, filed by Google..
  3. David Belanger

    Google AI, Boston, United States
    Competing interests
    David Belanger, performed research as part of their employment at Google LLC. Google is a technology company that sells machine learning services as part of its business. Portions of this work are covered by US patent WO2020210591A1, filed by Google..
  4. Lucy J Colwell

    Google AI, Boston, United States
    Competing interests
    Lucy J Colwell, performed research as part of their employment at Google LLC. Google is a technology company that sells machine learning services as part of its business. Portions of this work are covered by US patent WO2020210591A1, filed by Google..

Funding

Google

  • Theo Sanderson
  • Maxwell L Bileschi
  • David Belanger
  • Lucy J Colwell

The authors were employed by the funder while completing this work.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Version history

  1. Preprint posted: September 23, 2021 (view preprint)
  2. Received: June 10, 2022
  3. Accepted: February 24, 2023
  4. Accepted Manuscript published: February 27, 2023 (version 1)
  5. Version of Record published: March 30, 2023 (version 2)

Copyright

© 2023, Sanderson et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 7,107
    views
  • 882
    downloads
  • 53
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Theo Sanderson
  2. Maxwell L Bileschi
  3. David Belanger
  4. Lucy J Colwell
(2023)
ProteInfer, deep neural networks for protein functional inference
eLife 12:e80942.
https://doi.org/10.7554/eLife.80942

Share this article

https://doi.org/10.7554/eLife.80942

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Andrea I Luppi, Pedro AM Mediano ... Emmanuel A Stamatakis
    Research Article

    How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a ‘synergistic global workspace’, comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain’s default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Ardalan Naseri, Degui Zhi, Shaojie Zhang
    Research Article Updated

    Runs-of-homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE (runs-of-homozygous diplotype cluster enumerator), to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number of individuals, in large cohorts. ROH-DICE identified over 1 million ROH diplotypes that span over 100 single nucleotide polymorphisms (SNPs) and are shared by more than 100 UK Biobank participants. Moreover, we found significant associations of clustered ROH diplotypes across the genome with various self-reported diseases, with the strongest associations found between the extended human leukocyte antigen (HLA) region and autoimmune disorders. We found an association between a diplotype covering the homeostatic iron regulator (HFE) gene and hemochromatosis, even though the well-known causal SNP was not directly genotyped or imputed. Using a genome-wide scan, we identified a putative association between carriers of an ROH diplotype in chromosome 4 and an increase in mortality among COVID-19 patients (p-value = 1.82 × 10−11). In summary, our ROH-DICE method, by calling out large ROH diplotypes in a large outbred population, enables further population genetics into the demographic history of large populations. More importantly, our method enables a new genome-wide mapping approach for finding disease-causing loci with multi-marker recessive effects at a population scale.