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gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration.
Orvis J, et al. Nat Methods. 2021 Jun 25.
doi: 10.1038/s41592-021-01200-9
PMID:
34172972
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NeMO Analytics: A Curated Compendium of Transcriptomic Data for the Exploration of Neocortical Development
Shreyash Sonthalia, Brian Herb, Ricky S. Adkins, Joshua Orvis, Guangyan Li, Xiangyu Liao, Qingjie Yu,
Xoel Mato Blanco, Alex Casella, Jinrui Liu, Genevieve Stein-O’Brien, Brian Caffo,
Ronna Hertzano, Anup Mahurkar, Jin-Chong Xu, Jesse Gillis, Jonathan Werner, Shaojie Ma, Suel-Kee Kim, Nicola
Micali, Nenad Sestan, Pasko Rakic, Gabriel Santpere, Seth A. Ament, Carlo Colantuoni
To enable researchers to more fully harness the collective discovery potential of multi-omic data in the public domain, we have assembled gene-level transcriptomic data from ~200 studies of neocortical development and in vitro models. Applying joint matrix decomposition to mouse, macaque and human data, we define transcriptome dynamics that are conserved across neocortical neurogenesis and identify a program that emerges in ventricular progenitors, is later expressed in neurogenic outer, or basal, radial glia of primates, but is limited to gliogenic precursors in the rodent. Decomposition of adult human neocortical data identified layer-specific signatures in excitatory neurons, enabling the charting of their developmental emergence and protracted maturation, which is in stark contrast to the early peaking expression of layer-defining transcription factors. Interrogation of data from cerebral organoids demonstrated that while broad elements of in vivo development are recapitulated in vitro, many layer-specific transcriptomic programs in neuronal maturation are absent. We invite cell biologists without coding expertise to use NeMO Analytics in their research and to fuel it with their own emerging data.
Joint decomposition of scRNA-seq data in the NeMO Analytics neocortical development
data collection
Schematic of NeMO Analytics data resources employed in conjunction with joint decomposition
and transfer learning approaches. This is an outline of specific analyses in this report as
well as a description of a general approach we invite others to take on. Analysis-ready
datasets and detailed sample metadata can be downloaded from NeMO Analytics and analyzed
offline. Elements learned from joint decomposition can then be uploaded to NeMO Analytics
to explore their dynamics across the broad data collection. In this flow, the offline
analysis could be any exploratory technique applied to mutli-omics data matrices that
produces gene signatures in the form of simple lists or quantitative loadings, e.g. PCA,
clustering, or differential expression analysis.
Exploring data collections and gene signatures with projection analysis
The central notion behind our approach is to:
Create a comprehensive compendium of transcriptomic datasets focused on neocortical
development: "
Transcriptomic data collections
" below. And:
Apply diverse matrix decomposition approaches (SJD) to define robust transcriptomic
dynamics that are shared across carefully selected datasets: "
Gene signatures
" below. Followed by:
Molecular dissection of the broad transcriptomic data collections (1) by projection into
gene signatures (2): Table of ”
Projection links
“ below.
1. Transcriptomic data collections (profiles) focused on the neocortex in NeMO Analytics
Figure 1:
scRNA-seq in mouse, macaque and human mid-gestational neocortex
Figure 2:
Bulk, single-cell and spatial transcriptomic data in mouse, macaque and human mid-gestational neocortex
NeocortexDevoHsInVivo:
in vivo data from the developing human neocortex
NeocortexDevoHsInVitro:
cerebral organoids neural differentiation in human stem cell models of the neocortex
NeocortexDevoMmInVivo:
in vivo data from the developing mouse neocortex
NeocortexDevoNHPInVivo:
in vivo data from the developing macaque, marmoset, and chimpanzee neocortex
NeocortexEvoDevo:
selected subset of in vivo datasets from mouse, macaque and human developing neocortex
AdultNeoctxLayers:
in vivo data from the mature human neocortex and spatial transcriptomics across species
MammalianEmbryo:
mammalian embryo development and the emergence of the neural lineage and telencephalon
2. Gene signatures derived from joint matrix decomposition of neocortical data
MammCtxDev.jNMF.p7:
Seven patterns defining conserved transcriptomic dynamics across scRNA-seq from mouse, macaque, and human neocortical neurogenesis (Figures 1 & 2, Sonthalia et al, where p5=RG/cycling, p4=IPC, p7=nascent neuron, p2=maturing neuron).
MammCtxDev.jNMF.p40:
Forty patterns defining conserved transcriptomic dynamics across scRNA-seq from mouse, macaque, and human neocortical neurogenesis (Figure 3, Sonthalia et al, where p27=oRG).
HsCtxLayer.jNMF.p20:
Twenty patterns defining shared transcriptomic signatures in snRNA-seq from adult human neocortical neurons from layer-specific microdissections across 8 neocortical regions and 5 donors (Figures 4 & 5, Sonthalia et al, where p1=subplate/L6b, p9=L6CT, p15=L6IT, p13=L5/6NP, p6=L5IT, p19=L4primate-specific, p4=L4conserved, p17=L2/3, p7=L2).
CellCycleGenes:
Two groups of genes - those expressed specifically in S- or G2M-phase of the cell cycle (from Seurat).
CtxDiseaseGeneLists:
Many neocortical disease risk gene lists (from MatoBlanco et al 2024).
3. Projection links to explore gene signatures across the NeMO Analytics data collections
Each cell in the table links to the projection of 1 of the NeMO analytics data collections described
above into 1 of the gene signatures described above, allowing the exploration of each of the gene
signatures as it change across the millions of samples in the NeMO Analytics neocortical data
collections (the first column of links can be used to view the expression of individual genes across
the data collections). Red highlighted cells indicate specific [data collection :: gene signature]
combinations of particular interest.
Gene signatures
Individual gene links
MammCtxDev.jNMF.p7
MammCtxDev.jNMF.p40
HsCtxLayer.jNMF.p20
CellCycleGenes
CtxDiseaseGeneLists
Transcriptome data collections
Figure 1
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Figure 2
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NeocortexDevoHsInVivo
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NeocortexDevoHsInVitro
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NeocortexDevoMmInVivo
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NeocortexDevoNHPInVivo
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NeocortexEvoDevo
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AdultNeoctxLayers
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MammalianEmbryo
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We invite researchers to add their own datasets and gene signatures to this environment to
explore their own data, ideas & hypotheses and to expand the discovery potential of this
shared community research resource:
Data uploading
Gene cart uploading
Github site or this publication (with NeMO Analytics tutorials and SJD code)
Colantuoni Collaborative - Neocortical Development