BrainImageR: spatiotemporal gene set analysis referencing the human brain
Open accessPublished version of a preprint
Abstract
Motivation: Neuronal analyses such as transcriptomics, epigenetics and genome-wide association studies must be assessed in the context of the human brain to generate biologically meaningful inferences. It is often difficult to access primary human brain tissue; therefore, approximations are made using alternative sources such as peripheral tissues or in vitro-derived neurons. Gene sets from these studies are then assessed for their association with the post-mortem human brain. However, most analyses of post-mortem datasets are achieved by building new computational tools each time in-house, which can cause discrepancies from study to study. The field is in need of a user-friendly tool to examine spatiotemporal expression with respect to the postmortem brain. Such a tool will be of use in the molecular interrogation of neurological and psychiatric disorders, with direct advantages for the disease-modeling and human genetics communities. Results: We have developed brainImageR, an R package that calculates both the spatial and temporal association of a dataset with post-mortem human brain. BrainImageR identifies anatomical regions enriched for candidate gene set expression. It further predicts the developmental time point of the sample, a task that has become increasingly important in the field of in vitro neuronal modeling. These functionalities of brainImageR enable a quick and efficient characterization of a given dataset across normal human brain development. Availability and implementation: BrainImageR is released under the Creative Commons CC BY-SA 4.0 license and can be accessed directly at brainimager.salk.edu or the R code can be downloaded through github at https://github.com/saralinker/brainImageR.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Microglial gene expression was enriched in multiple brain regions, some of which are implicated in Alzheimer's disease (AD), such as the parahippocampal gyrus, temporal pole, fusiform gyrus, and amygdalohippocampal transition zone.
“Interestingly, microglial gene expression was enriched in multiple brain regions, some of which are implicated in Alzheimer's disease (AD), such as the parahippocampal gyrus, temporal pole, fusiform gyrus, and amygdalohippocampal transition zone.”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [14]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Classification and Regression by randomForest
Liaw, A. I., & Wiener, M. C. (2007) · Cited by 18,594 · see citing works
An anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083 · see citing works
Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture
Paşca, A. M., Sloan, S. A., Clarke, L. E., Tian, Y., Makinson, C. D., Huber, N., Kim, C. H., Park, J.-Y., O'Rourke, N. A., Nguyen, K. D., et al. (2015) · Nature Methods · doi:10.1038/nmeth.3415 · Cited by 1,609 · see citing works
A survey of human brain transcriptome diversity at the single cell level
Darmanis, S., Sloan, S. A., Zhang, Y., Enge, M., Caneda, C., Shuer, L. M., Hayden Gephart, M. G., Barres, B. A., & Quake, S. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1507125112 · Cited by 1,401 · see citing works
Transcriptional landscape of the prenatal human brain
Miller, J. A., Ding, S.-L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., et al. (2014) · Nature · doi:10.1038/nature13185 · Cited by 1,325 · see citing works
Human cerebral organoids recapitulate gene expression programs of fetal neocortex development
Camp, J. G., Badsha, F., Florio, M., Kanton, S., Gerber, T., Wilsch-Bräuninger, M., Lewitus, E., Sykes, A., Hevers, W., Lancaster, M., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520760112 · Cited by 1,130 · see citing works
Pollen, A. A., Nowakowski, T. J., Shuga, J., Wang, X., Leyrat, A. A., Lui, J. H., Li, N., Szpankowski, L., Fowler, B., Chen, P., et al. (2014) · Nature Biotechnology · doi:10.1038/nbt.2967 · Cited by 920 · see citing works
Mertens, J., Paquola, A. C. M., Ku, M., Hatch, E., Böhnke, L., Ladjevardi, S., McGrath, S., Campbell, B., Lee, H., Herdy, J. R., et al. (2015) · Cell Stem Cell · doi:10.1016/j.stem.2015.09.001 · Cited by 765 · see citing works
Self-citationHuman pluripotent stem cell-derived neural constructs for predicting neural toxicity
Schwartz, M. P., Hou, Z., Propson, N. E., Zhang, J., Engstrom, C. J., Costa, V. S., Jiang, P., Nguyen, B. K., Bolin, J. M., Daly, W., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516645112 · Cited by 325 · see citing works
A Quantitative Framework to Evaluate Modeling of Cortical Development by Neural Stem Cells
Stein, J. L., de la Torre-Ubieta, L., Tian, Y., Parikshak, N. N., Hernández, I. A., Marchetto, M. C., Baker, D. K., Lu, D., Hinman, C. R., Lowe, J. K., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.05.035 · Cited by 201 · see citing works
Self-citationGrote, S., Prüfer, K., Kelso, J. F., & Dannemann, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw392 · Cited by 50 · see citing works
cerebroViz: an R package for anatomical visualization of spatiotemporal brain data
Bahl, E., Koomar, T., & Michaelson, J. J. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw726 · Cited by 41 · see citing works
Distribution of cellular HSV-1 receptor expression in human brain
Lathe, R., & Haas, J. (2016) · Journal of NeuroVirology · doi:10.1007/s13365-016-0504-x · Cited by 36 · see citing works
Li, Y., Wang, R., Qiao, N., Peng, G., Zhang, K., Tang, K., Han, J. J., & Jing, N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.796383 · Cited by 35 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Species-specific maturation profiles of human, chimpanzee and bonobo neural cells
Marchetto, M. C., Hrvoj-Mihic, B., Kerman, B. E., Yu, D. X., Vadodaria, K. C., Linker, S. B., Narvaiza, I., Santos, R., Denli, A. M., Mendes, A. P., et al. (2019) · eLife · doi:10.7554/elife.37527 · Cited by 132 · see citing works
Self-citationThe Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease
Bonham, L. W., Sirkis, D. W., & Yokoyama, J. S. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01170 · Cited by 83 · see citing works
- Authors
- Linker, S. B., Hsu, J. Y., Pfaff, A., Amatya, D., Ko, S.-M., Voter, S., Wong, Q., & Gage, F. H.
- Affiliations
- Salk Institute for Biological Studies (US)
- Corresponding author
- Linker, Sara B
- Gage, Fred H
- Venue
- Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-07-13
- Volume
- 35
- Issue
- 2
- Pages
- 343-345
- ISSN
- 1367-4803 (ISSN-L)
- 1367-4811
- PMC
- PMC6657270
- OpenAlex
- W2949573613
- Cited by
- 7
- References
- 14
- Citations by year
- 2024: 1 · 2022: 1 · 2020: 2 · 2019: 3
- FWCI
- 0.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Bioinformatics (publishedVersion, cc-by-sa)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Lynn and Edward Streim
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Keywords
- postmortem brain, spatiotemporal gene expression, gene set enrichment analysis, brain development, in vitro neuronal model, peripheral tissues, transcriptomics, epigenetics, genome-wide association study, R package, neuropsychiatric disorders
- MeSH terms
- Brain, Humans, Neurons, Software, Computational Biology, Epigenesis, Genetic, Genome-Wide Association Study, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review