Constructing and optimizing 3D atlases from 2D data with application to the developing mouse brain

  1. David M Young
  2. Siavash Fazel Darbandi
  3. Grace Schwartz
  4. Zachary Bonzell
  5. Deniz Yuruk
  6. Mai Nojima
  7. Laurent C Gole
  8. John LR Rubenstein
  9. Weimiao Yu
  10. Stephan J Sanders  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Agency for Science, Technology and Research, Singapore

Abstract

3D imaging data necessitate 3D reference atlases for accurate quantitative interpretation. Existing computational methods to generate 3D atlases from 2D-derived atlases result in extensive artifacts, while manual curation approaches are labor-intensive. We present a computational approach for 3D atlas construction that substantially reduces artifacts by identifying anatomical boundaries in the underlying imaging data and using these to guide 3D transformation. Anatomical boundaries also allow extension of atlases to complete edge regions. Applying these methods to the eight developmental stages in the Allen Developing Mouse Brain Atlas (ADMBA) led to more comprehensive and accurate atlases. We generated imaging data from fifteen whole mouse brains to validate atlas performance and observed qualitative and quantitative improvement (37% greater alignment between atlas and anatomical boundaries). We provide the pipeline as the MagellanMapper software and the eight 3D reconstructed ADMBA atlases. These resources facilitate whole-organ quantitative analysis between samples and across development.

Data availability

The full 3D generated atlases and wild-type brain images are being deposited with the Human Brain Project EBRAINS data platform. All data analyses are included in the manuscript and supporting files.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. David M Young

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Siavash Fazel Darbandi

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Grace Schwartz

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Zachary Bonzell

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Deniz Yuruk

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Mai Nojima

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Laurent C Gole

    Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  8. John LR Rubenstein

    Department of Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4414-7667
  9. Weimiao Yu

    Institute of Molecular and Cellular Biology, Agency for Science, Technology and Research, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  10. Stephan J Sanders

    Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, United States
    For correspondence
    stephan.sanders@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9112-5148

Funding

Brain and Behavior Research Foundation (NARSAD Young Investigator Grant)

  • Stephan J Sanders

National Institute of Mental Health (U01 MH122681)

  • Stephan J Sanders

National Institute of Mental Health (R01 MH109901)

  • Stephan J Sanders

National Institute of Neurological Disorders and Stroke (R01 NS099099)

  • John LR Rubenstein

The authors declare that the funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Joseph G Gleeson, Howard Hughes Medical Institute, The Rockefeller University, United States

Ethics

Animal experimentation: All procedures and animal care were approved and performed in accordance with institutional guidelines from the University of California San Francisco Laboratory Animal Research Center (LARC). All animal handling complied with the approved Institutional Animal Care and Use Committee (IACUC) protocol (AN180174-02) at the University of California San Francisco.

Version history

  1. Received: July 24, 2020
  2. Accepted: February 10, 2021
  3. Accepted Manuscript published: February 11, 2021 (version 1)
  4. Version of Record published: March 25, 2021 (version 2)

Copyright

© 2021, Young 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

  • 4,072
    views
  • 310
    downloads
  • 13
    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. David M Young
  2. Siavash Fazel Darbandi
  3. Grace Schwartz
  4. Zachary Bonzell
  5. Deniz Yuruk
  6. Mai Nojima
  7. Laurent C Gole
  8. John LR Rubenstein
  9. Weimiao Yu
  10. Stephan J Sanders
(2021)
Constructing and optimizing 3D atlases from 2D data with application to the developing mouse brain
eLife 10:e61408.
https://doi.org/10.7554/eLife.61408

Share this article

https://doi.org/10.7554/eLife.61408

Further reading

    1. Computational and Systems Biology
    2. Genetics and Genomics
    Weichen Song, Yongyong Shi, Guan Ning Lin
    Tools and Resources

    We propose a new framework for human genetic association studies: at each locus, a deep learning model (in this study, Sei) is used to calculate the functional genomic activity score for two haplotypes per individual. This score, defined as the Haplotype Function Score (HFS), replaces the original genotype in association studies. Applying the HFS framework to 14 complex traits in the UK Biobank, we identified 3619 independent HFS–trait associations with a significance of p < 5 × 10−8. Fine-mapping revealed 2699 causal associations, corresponding to a median increase of 63 causal findings per trait compared with single-nucleotide polymorphism (SNP)-based analysis. HFS-based enrichment analysis uncovered 727 pathway–trait associations and 153 tissue–trait associations with strong biological interpretability, including ‘circadian pathway-chronotype’ and ‘arachidonic acid-intelligence’. Lastly, we applied least absolute shrinkage and selection operator (LASSO) regression to integrate HFS prediction score with SNP-based polygenic risk scores, which showed an improvement of 16.1–39.8% in cross-ancestry polygenic prediction. We concluded that HFS is a promising strategy for understanding the genetic basis of human complex traits.

    1. Computational and Systems Biology
    Qianmu Yuan, Chong Tian, Yuedong Yang
    Tools and Resources

    Revealing protein binding sites with other molecules, such as nucleic acids, peptides, or small ligands, sheds light on disease mechanism elucidation and novel drug design. With the explosive growth of proteins in sequence databases, how to accurately and efficiently identify these binding sites from sequences becomes essential. However, current methods mostly rely on expensive multiple sequence alignments or experimental protein structures, limiting their genome-scale applications. Besides, these methods haven’t fully explored the geometry of the protein structures. Here, we propose GPSite, a multi-task network for simultaneously predicting binding residues of DNA, RNA, peptide, protein, ATP, HEM, and metal ions on proteins. GPSite was trained on informative sequence embeddings and predicted structures from protein language models, while comprehensively extracting residual and relational geometric contexts in an end-to-end manner. Experiments demonstrate that GPSite substantially surpasses state-of-the-art sequence-based and structure-based approaches on various benchmark datasets, even when the structures are not well-predicted. The low computational cost of GPSite enables rapid genome-scale binding residue annotations for over 568,000 sequences, providing opportunities to unveil unexplored associations of binding sites with molecular functions, biological processes, and genetic variants. The GPSite webserver and annotation database can be freely accessed at https://bio-web1.nscc-gz.cn/app/GPSite.