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Deconvolving the contributions of cell-type heterogeneity on cortical gene expression [article]

Ellis Patrick, Mariko Taga, Ayla Ergun, Bernard Ng, William Casazza, Maria Cimpean, Christina Yung, Julie A Schneider, David A Bennet, Chris Gaiteri, Philip L De Jager, Elizabeth M Bradshaw (+1 others)
2019 bioRxiv   pre-print
We demonstrate that several algorithms that rely on single-cell and cell-sorted data to define cell marker gene sets yield accurate relative and absolute estimates of constituent cell-type proportions.  ...  Complexity of cell-type composition has created much skepticism surrounding the interpretation of brain bulk-tissue transcriptomic studies.  ...  Accurately separating out the contributions of cell-type composition on gene expression, through a mathematical process known as deconvolution, should result in more accurate molecular measures of disease  ... 
doi:10.1101/566307 fatcat:npvgzz6pwrchlhz3tmowvsasdm

MRI-localized biopsies reveal subtype-specific differences in molecular and cellular composition at the margins of glioblastoma

B. J. Gill, D. J. Pisapia, H. R. Malone, H. Goldstein, L. Lei, A. Sonabend, J. Yun, J. Samanamud, J. S. Sims, M. Banu, A. Dovas, A. F. Teich (+6 others)
2014 Proceedings of the National Academy of Sciences of the United States of America  
Gene ontology analysis showed that the cell type-specific expression patterns were functionally distinct and highly enriched in genes associated with the corresponding cell phenotypes.  ...  Comparing the RNA-seq data from the GBM samples to that of nonneoplastic brain revealed that the differentially expressed genes are distributed across multiple cell types.  ...  (A) The heat map shows the expression of cell-type genes in the six cell types that were deconvolved from the NB and NE samples: High expression is yellow, and low expression is black.  ... 
doi:10.1073/pnas.1405839111 pmid:25114226 pmcid:PMC4151734 fatcat:ftsj5poirnaptbzrht5s7ashym

Spatiotemporal gene expression trajectories reveal developmental hierarchies of the human cortex

Tomasz J. Nowakowski, Aparna Bhaduri, Alex A. Pollen, Beatriz Alvarado, Mohammed A. Mostajo-Radji, Elizabeth Di Lullo, Maximilian Haeussler, Carmen Sandoval-Espinosa, Siyuan John Liu, Dmitry Velmeshev, Johain Ryad Ounadjela, Joe Shuga (+6 others)
2017 Science  
Systematic analyses of spatiotemporal gene expression trajectories during organogenesis have been challenging because diverse cell types at different stages of maturation and differentiation coexist in  ...  Together, our results support a mixed model of topographical, typological, and temporal hierarchies governing cell-type diversity in the developing human telencephalon, including distinct excitatory lineages  ...  ACKNOWLEDGMENTS The authors thank S. Wang SUPPLEMENTARY MATERIALS Materials and Methods Figs. S1 to S13 References (32-38) Tables S1 to S11  ... 
doi:10.1126/science.aap8809 pmid:29217575 pmcid:PMC5991609 fatcat:ghp3zsc7efh5hhpqcice4nrbli

Deep learning–based cell composition analysis from tissue expression profiles

Kevin Menden, Mohamed Marouf, Sergio Oller, Anupriya Dalmia, Daniel Sumner Magruder, Karin Kloiber, Peter Heutink, Stefan Bonn
2020 Science Advances  
We present Scaden, a deep neural network for cell deconvolution that uses gene expression information to infer the cellular composition of tissues.  ...  A single trained network reliably deconvolves bulk RNA-seq and microarray, human and mouse tissue expression data and leverages the combined information of multiple datasets.  ...  cells to select for the cell type c, and N total is the total number of cells contributing to one simulated RNA-seq sample (500, in this study).  ... 
doi:10.1126/sciadv.aba2619 pmid:32832661 pmcid:PMC7439569 fatcat:x7g5jrq4e5hopcb6ztjscsqi3a

Broad transcriptomic dysregulation across the cerebral cortex in ASD [article]

Jillian R Haney, Brie Wamsley, George T Chen, Sepideh Parhami, Prashant S Emani, Nathan Chang, Gil D Hoftman, Diego de Alba, Gaurav Kale, Gokul Ramaswami, Christopher L Hartl, Ting Jin (+10 others)
2020 bioRxiv   pre-print
Finally, using snRNA-seq, we determine that regional variation in the magnitude of transcriptomic dysregulation reflects changes in cellular proportion and cell-type-specific gene expression, particularly  ...  alterations.1-3 In ASD, upregulation of microglial, astrocyte, and immune signaling genes, downregulation of specific synaptic genes, and attenuation of regional gene expression differences are observed  ...  Cell vol. 155 1008-1021 (2013). 22 23. Patrick, E. et al. Deconvolving the contributions of cell-type heterogeneity on cortical gene 23 expression. PLoS Comput. Biol. 16, e1008120 (2020). 24 24.  ... 
doi:10.1101/2020.12.17.423129 fatcat:yobwvmsdjbdwfozzlfcepxglr4

Radial glia require PDGFD–PDGFRβ signalling in human but not mouse neocortex

Jan H. Lui, Tomasz J. Nowakowski, Alex A. Pollen, Ashkan Javaherian, Arnold R. Kriegstein, Michael C. Oldham
2014 Nature  
Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown.  ...  We further show that the expression domain of PDGFRß, the cognate receptor 6, 7 for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in  ...  We thank Joe DeYoung and the staff at the Southern California Genotyping Consortium at the University of California Los Angeles for microarray data generation.  ... 
doi:10.1038/nature13973 pmid:25391964 pmcid:PMC4231536 fatcat:56e4mos4vjc5xatr5yrmvw5zdm

Deep-learning-based cell composition analysis from tissue expression profiles [article]

Kevin Menden, Mohamed Marouf, Anupriya Dalmia, Peter Heutink, Stefan Bonn
2019 bioRxiv   pre-print
We present Scaden, a deep neural network for cell deconvolution that uses gene expression information to infer the cellular composition of tissues.  ...  Scaden's comprehensive software package is easy to use on novel as well as diverse existing expression datasets available in public resources, deepening the molecular and cellular understanding of developmental  ...  Acknowledgements 694 We would like to thank the people of the Genome Biology of Neurodegenerative  ... 
doi:10.1101/659227 fatcat:wsl5l5wpujh7dcimeuuekgemlm

Morphological study of embryonic Chd8+/− mouse brains using light-sheet microscopy

Harold F. Gómez, Leonie Hodel, Odyssé Michos, Dagmar Iber
2021 BMC Research Notes  
This study advocates the use of high-resolution microscopy technologies and multi-scale morphometric analyses of target brain regions to explore the etiology and cellular basis of Chd8 haploinsufficiency  ...  We report a detailed morphometric characterization of embryonic brain shapes and cortical neuroepithelial apical architecture.  ...  Shetty for providing the embryos. Moreover, we acknowledge Richard S. Smith for his expert advice on extending MorphoGraphX to enable aspect ratio quantifications of segmented cell outlines.  ... 
doi:10.1186/s13104-020-05436-0 pmid:33436073 fatcat:eqhlemhcebbenmg6rix6s4ydpm

Cell autonomous defects in cortical development revealed by two-color chimera analysis

Adam V. Kwiatkowski, Craig C. Garner, W. James Nelson, Frank B. Gertler
2009 Molecular and Cellular Neuroscience  
We observed little difference between the ability of control and Ena/VASP-deficient cells to contribute to cortical organization during development.  ...  A complex program of cell intrinsic and extrinsic signals guide cortical development.  ...  Acknowledgments Doug Rubinson designed and constructed the original pLL4.4 vector.  ... 
doi:10.1016/j.mcn.2009.01.008 pmid:19386231 pmcid:PMC2684858 fatcat:ps4iscy7svharmtnaud6yofi2m

Convergent molecular, cellular, and neural signatures of major depressive disorder [article]

Kevin M Anderson, Meghan A Collins, Ru Kong, Kacey Fang, Jingwei Li, Tong He, Adam M Chekroud, B.T. Thomas Yeo, Avram J Holmes
2020 bioRxiv   pre-print
Integrative analyses incorporated measures of cortical gene expression, post-mortem patient transcriptional data, depression GWAS, and single-cell transcription.  ...  Major depressive disorder emerges from the complex interactions of biological systems that span across genes and molecules through cells, circuits, networks, and behavior.  ...  depression, normalized for the number of genes in a given cell-type set (i.e.  ... 
doi:10.1101/2020.02.10.942227 fatcat:on2hg4dcsfgsngaojcohtlvkcu

Computational deconvolution of genome wide expression data from Parkinson's and Huntington's disease brain tissues using population-specific expression analysis

Alberto Capurro, Liviu-Gabriel Bodea, Patrick Schaefer, Ruth Luthi-Carter, Victoria M. Perreau
2015 Frontiers in Neuroscience  
However, many studies utilize heterogeneous tissue samples consisting of multiple cell types, all of which contribute to global gene expression values, confounding biological interpretation of the data  ...  PSEA estimates cell-type-specific expression values using reference expression measures, which in the case of brain tissue comprises mRNAs with cell-type-specific expression in neurons, astrocytes, oligodendrocytes  ...  The method deconvolves brain expression heterogeneity by linear regression modeling to resolve cell-type-specific expression changes.  ... 
doi:10.3389/fnins.2014.00441 pmid:25620908 pmcid:PMC4288238 fatcat:ho2z6gqt5fgkhjsvhfezfazpe4

Morphological and genomic shifts in mole-rat 'queens' increase fecundity but reduce skeletal integrity

Rachel A Johnston, Philippe Vullioud, Jack Thorley, Henry Kirveslahti, Leyao Shen, Sayan Mukherjee, Courtney M Karner, Tim Clutton-Brock, Jenny Tung
2021 eLife  
Here, we investigate the consequences of breeding for skeletal morphology and gene regulation in highly cooperative Damaraland mole-rats.  ...  Together, our results show that, as in eusocial insects, reproductive division of labor in mole-rats leads to gene regulatory rewiring and extensive morphological plasticity.  ...  To assess whether cell type heterogeneity accounts for queen-538 associated differential expression, we used CIBERSORT (RRID:SCR_016955) to deconvolve 539 the proportion of component cell types from the  ... 
doi:10.7554/elife.65760 pmid:33843584 pmcid:PMC8104968 fatcat:5q2flcyymje6tjnulpq3rexesi

Comparison of Kidney Transcriptomic Profiles of Early and Advanced Diabetic Nephropathy Reveals Potential New Mechanisms for Disease Progression

Ying Fan, Zhengzi Yi, Vivette D. D'Agati, Zeguo Sun, Fang Zhong, Weijia Zhang, Jiejun Wen, Ting Zhou, Ze Li, Li He, Qunzi Zhang, Kyung Lee (+2 others)
2019 Diabetes  
Correlation with estimated glomerular filtration rate (eGFR) identified genes in the pathways of iron transport and cell differentiation to be positively associated with eGFR, while those in the immune  ...  Our study thus provides potential molecular mechanisms for DN progression and association of differential gene expression with the functional and structural changes observed in patients with early and  ...  While the isolation of glomeruli would yield more specific information on glomerular cells, the data will nevertheless represent those of heterogeneous glomerular cell types.  ... 
doi:10.2337/db19-0204 pmid:31578193 pmcid:PMC6868471 fatcat:jcucvxwrx5ezrdca5uwb7ygzfi

Revisiting an Expression Dataset of Discordant Inflammatory Bowel Disease Twin Pairs Using a Mutation Burden Test Reveals CYP2C18 as a Novel Marker

Juan Du, Jie Yin, Haojie Du, Jiawei Zhang
2021 Frontiers in Genetics  
The differentially expressed genes were significantly enriched in a gene set associated with cortical and medullary thymocytes.  ...  Through deconvolution of the immune cell populations and tissue expression specificity, we refined the candidate genes for susceptibility to ulcerative colitis.  ...  Deconvolution of the Tissue Specificity of the DEGs and Refinement of Candidate Genes To refine the candidate genes involved in IBD, we deconvolve the tissue expression specificity of the DEGs that do  ... 
doi:10.3389/fgene.2021.680125 fatcat:ibfkk5vqabho7oaojxxahgazem

Genome-wide Spatial Expression Profiling in FFPE Tissues [article]

Eva Gracia Villacampa, Ludvig Larsson, Linda Kvastad, Alma Andersson, Joseph Carlson, Joakim Lundeberg
2020 bioRxiv   pre-print
First, we conducted expression profiling and cell type mapping in coronal sections from the mouse brain to demonstrate the method's capability to delineate anatomical regions from a molecular perspective  ...  mechanisms in heterogeneous clinical samples.  ...  Thus, to make an informed statement regarding certain cell types' arrangement within the tissue, based on the spatial transcriptomics data, one must first deconvolve the gene expression profiles.  ... 
doi:10.1101/2020.07.24.219758 fatcat:2xdvdh4wnramdaricwhrezcnc4
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