scholarly journals Replicability of spatial gene expression atlas data from the adult mouse brain

2020 ◽  
Author(s):  
Shaina Lu ◽  
Cantin Ortiz ◽  
Daniel Fürth ◽  
Stephan Fischer ◽  
Konstantinos Meletis ◽  
...  

AbstractBackgroundSpatial gene expression is particularly interesting in the mammalian brain, with the potential to serve as a link between many data types. However, as with any type of expression data, cross-dataset benchmarking of spatial data is a crucial first step. Here, we assess the replicability, with reference to canonical brain sub-divisions, between the Allen Institute’s in situ hybridization data from the adult mouse brain (ABA) and a similar dataset collected using Spatial Transcriptomics (ST). With the advent of tractable spatial techniques, for the first time we are able to benchmark the Allen Institute’s whole-brain, whole-transcriptome spatial expression dataset with a second independent dataset that similarly spans the whole brain and transcriptome.ResultsWe use LASSO, linear regression, and correlation-based feature selection in a supervised learning framework to classify expression samples relative to their assayed location. We show that Allen reference atlas labels are classifiable using transcription, but that performance is higher in the ABA than ST. Further, models trained in one dataset and tested in the opposite dataset do not reproduce classification performance bi-directionally. Finally, while an identifying expression profile can be found for a given brain area, it does not generalize to the opposite dataset.ConclusionsIn general, we found that canonical brain area labels are classifiable in gene expression space within dataset and that our observed performance is not merely reflecting physical distance in the brain. However, we also show that cross-platform classification is not robust. Emerging spatial datasets from the mouse brain will allow further characterization of cross-dataset replicability.

PLoS Biology ◽  
2021 ◽  
Vol 19 (7) ◽  
pp. e3001341
Author(s):  
Shaina Lu ◽  
Cantin Ortiz ◽  
Daniel Fürth ◽  
Stephan Fischer ◽  
Konstantinos Meletis ◽  
...  

High-throughput, spatially resolved gene expression techniques are poised to be transformative across biology by overcoming a central limitation in single-cell biology: the lack of information on relationships that organize the cells into the functional groupings characteristic of tissues in complex multicellular organisms. Spatial expression is particularly interesting in the mammalian brain, which has a highly defined structure, strong spatial constraint in its organization, and detailed multimodal phenotypes for cells and ensembles of cells that can be linked to mesoscale properties such as projection patterns, and from there, to circuits generating behavior. However, as with any type of expression data, cross-dataset benchmarking of spatial data is a crucial first step. Here, we assess the replicability, with reference to canonical brain subdivisions, between the Allen Institute’s in situ hybridization data from the adult mouse brain (Allen Brain Atlas (ABA)) and a similar dataset collected using spatial transcriptomics (ST). With the advent of tractable spatial techniques, for the first time, we are able to benchmark the Allen Institute’s whole-brain, whole-transcriptome spatial expression dataset with a second independent dataset that similarly spans the whole brain and transcriptome. We use regularized linear regression (LASSO), linear regression, and correlation-based feature selection in a supervised learning framework to classify expression samples relative to their assayed location. We show that Allen Reference Atlas labels are classifiable using transcription in both data sets, but that performance is higher in the ABA than in ST. Furthermore, models trained in one dataset and tested in the opposite dataset do not reproduce classification performance bidirectionally. While an identifying expression profile can be found for a given brain area, it does not generalize to the opposite dataset. In general, we found that canonical brain area labels are classifiable in gene expression space within dataset and that our observed performance is not merely reflecting physical distance in the brain. However, we also show that cross-platform classification is not robust. Emerging spatial datasets from the mouse brain will allow further characterization of cross-dataset replicability ultimately providing a valuable reference set for understanding the cell biology of the brain.


2019 ◽  
Author(s):  
Cantin Ortiz ◽  
Jose Fernandez Navarro ◽  
Aleksandra Jurek ◽  
Antje Märtin ◽  
Joakim Lundeberg ◽  
...  

AbstractBrain maps are essential for integrating information and interpreting the structure-function relationship of circuits and behavior. We aimed to generate a systematic classification of the adult mouse brain organization based on unbiased extraction of spatially-defining features. Applying whole-brain spatial transcriptomics, we captured the gene expression signatures to define the spatial organization of molecularly discrete subregions. We found that the molecular code contained sufficiently detailed information to directly deduce the complex spatial organization of the brain. This unsupervised molecular classification revealed new area- and layer-specific subregions, for example in isocortex and hippocampus, and a new division of striatum. The whole-brain molecular atlas further supports the identification of the spatial origin of single neurons using their gene expression profile, and forms the foundation to define a minimal gene set - a brain palette – that is sufficient to spatially annotate the adult brain. In summary, we have established a new molecular atlas to formally define the identity of brain regions, and a molecular code for mapping and targeting of discrete neuroanatomical domains.


2000 ◽  
Vol 97 (20) ◽  
pp. 11038-11043 ◽  
Author(s):  
R. Sandberg ◽  
R. Yasuda ◽  
D. G. Pankratz ◽  
T. A. Carter ◽  
J. A. Del Rio ◽  
...  

2020 ◽  
Vol 225 (7) ◽  
pp. 2045-2056
Author(s):  
Ilias Kalafatakis ◽  
Konstantinos Kalafatakis ◽  
Alexandros Tsimpolis ◽  
Nikos Giannakeas ◽  
Markos Tsipouras ◽  
...  

2005 ◽  
Vol 102 (29) ◽  
pp. 10357-10362 ◽  
Author(s):  
M. A. Zapala ◽  
I. Hovatta ◽  
J. A. Ellison ◽  
L. Wodicka ◽  
J. A. Del Rio ◽  
...  

2008 ◽  
Vol 9 (1) ◽  
pp. 153 ◽  
Author(s):  
Christopher Lau ◽  
Lydia Ng ◽  
Carol Thompson ◽  
Sayan Pathak ◽  
Leonard Kuan ◽  
...  

Nature ◽  
2006 ◽  
Vol 445 (7124) ◽  
pp. 168-176 ◽  
Author(s):  
Ed S. Lein ◽  
Michael J. Hawrylycz ◽  
Nancy Ao ◽  
Mikael Ayres ◽  
Amy Bensinger ◽  
...  

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