Whole-brain comparison of rodent and human brains using spatial transcriptomics
- University of Toronto, Canada
- Mouse Imaging Centre, Canada
- Hospital for Sick Children, Canada
- National Institute of Mental Health, United States
- Radboud University Nijmegen, Netherlands
- University of Oxford, United Kingdom
Abstract
The ever-increasing use of mouse models in preclinical neuroscience research calls for an improvement in the methods used to translate findings between mouse and human brains. Previously we showed that the brains of primates can be compared in a direct quantitative manner using a common reference space built from white matter tractography data (Rogier B. Mars et al., 2018b). Here we extend the common space approach to evaluate the similarity of mouse and human brain regions using openly accessible brain-wide transcriptomic data sets. We show that mouse-human homologous genes capture broad patterns of neuroanatomical organization, but that the resolution of cross-species correspondences can be improved using a novel supervised machine learning approach. Using this method, we demonstrate that sensorimotor subdivisions of the neocortex exhibit greater similarity between species, compared with supramodal subdivisions, and that mouse isocortical regions separate into sensorimotor and supramodal clusters based on their similarity to human cortical regions. We also find that mouse and human striatal regions are strongly conserved, with the mouse caudoputamen exhibiting an equal degree of similarity to both the human caudate and putamen.
Data availability
The Allen Mouse Brain Atlas and Allen Human Brain Atlas data sets are openly accessible and can be downloaded from the Allen Institute's API (http://api.brain-map.org). All of the code and additional data needed to generate this analysis, including figures and manuscript, is accessible at https://github.com/abeaucha/MouseHumanTranscriptomicSimilarity/
Article and author information
Author details
Funding
Canadian Institutes of Health Research (Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships (GSD-165737))
- Antoine Beauchamp
Wellcome Trust (203139/Z/16/Z)
- Rogier B Mars
- Jason P Lerch
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Metrics
-
- 6,017
- views
-
- 616
- downloads
-
- 52
- 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)
Whole-brain comparison of rodent and human brains using spatial transcriptomics
eLife 11:e79418.
https://doi.org/10.7554/eLife.79418
Further reading
-
- Evolutionary Biology
- Neuroscience
The first complete 3D reconstruction of the compound eye of a minute wasp species sheds light on the nuts and bolts of size reduction.
-
- Evolutionary Biology
- Genetics and Genomics
Copy number variants (CNVs) are an important source of genetic variation underlying rapid adaptation and genome evolution. Whereas point mutation rates vary with genomic location and local DNA features, the role of genome architecture in the formation and evolutionary dynamics of CNVs is poorly understood. Previously, we found the GAP1 gene in Saccharomyces cerevisiae undergoes frequent amplification and selection in glutamine-limitation. The gene is flanked by two long terminal repeats (LTRs) and proximate to an origin of DNA replication (autonomously replicating sequence, ARS), which likely promote rapid GAP1 CNV formation. To test the role of these genomic elements on CNV-mediated adaptive evolution, we evolved engineered strains lacking either the adjacent LTRs, ARS, or all elements in glutamine-limited chemostats. Using a CNV reporter system and neural network simulation-based inference (nnSBI) we quantified the formation rate and fitness effect of CNVs for each strain. Removal of local DNA elements significantly impacts the fitness effect of GAP1 CNVs and the rate of adaptation. In 177 CNV lineages, across all four strains, between 26% and 80% of all GAP1 CNVs are mediated by Origin Dependent Inverted Repeat Amplification (ODIRA) which results from template switching between the leading and lagging strand during DNA synthesis. In the absence of the local ARS, distal ones mediate CNV formation via ODIRA. In the absence of local LTRs, homologous recombination can mediate gene amplification following de novo retrotransposon events. Our study reveals that template switching during DNA replication is a prevalent source of adaptive CNVs.
