Spatial transcriptomics on an expanded dataset at the brain-electrode interface: exploration of variability and identification of novel biomarkers.
The 4 matches
- [1] § Materials and methods › Data analysis and computational methods › Cell type-specific association of DEGs ↔ coreJointNMF.m, lines 1–52 · score 0.89 · joint NMF, reactivity gene distribution, Pearson correlation, spatial spots, NMF factors, OPC
- [2] § Results › Variance of top differentially expressed genes (DEGs) near the device across samples ↔ coreNMF.m, lines 43–92 · score 0.56 · S100a9, Il1b, Gpnmb, Spp1, Cxcl2, Slpi
- [3] § Results › Differentially expressed genes (DEGs) between and within 1 and 6-week implants ↔ coreJointNMF.m, lines 1–52 · score 0.53 · S100a9, Ctsk, Ighm, Hmox1, Gpnmb, Serping1
- [4] § Results › Differentially expressed genes (DEGs) between and within 1 and 6-week implants ↔ coreNMF.m, lines 43–92 · score 0.51 · S100a9, Ctsk, Ighm, Hmox1, Gpnmb, Serping1
Paper
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The authors' code
MATLAB · 250 lines · 8.6 KB · no license · 2 matches
- % Joint NMF analysis across grouped datasets
- % Pools all spatial spots within each time point group, runs a single
- % group-level NMF factorization, and computes Pearson correlation and
- % cosine similarity between NMF factors and reactivity gene distributions.
- % --- Configuration ---
- sampleDir = '/home/anirban/ubssd/BhanvaPaper_NMF';
- % Sample groups
- datasets_1week = {'1weekB', '1weekC', '1weekD', '1weekE', '1weekF', '1weekG', '1weekH'};
- datasets_6week = {'6weekB', '6weekC', '6weekF', '6weekG', '6weekH', '6weekI', '6weekJ'};
- % Reactivity genes per group
- %genes_1week = {'Cxcl3', 'Cxcl2', 'Ccl2', 'Il1b', 'Slpi', 'S100a9', ...
- % 'Hmox1', 'Lgals3', 'Gpnmb', 'Spp1', 'Ighm', 'Ctsk'};
- genes_1week = {'S100a4', 'S100a9', 'Cxcl3', 'Cxcl2', 'Ccl2', 'Il1b',...
- 'Hmox1', 'Lgals3', 'Gpnmb', 'Spp1','Ighm', 'Ctsk','Slpi'};
- genes_6week = {'Spp1', 'A2m', 'Lgals3', 'Gpnmb', 'S100a4', 'Serping1', ...
- 'Vim', 'Lyz2', 'S100a6', 'S100a9', 'Slpi', 'Ccl6', ...
- 'Hmox1', 'Il1b', 'Cxcl3', 'Il1rn', 'Srgn', 'Ccl2', 'Cxcl2'};
- % NMF rank per cell type: [Astrocytes, Neurons, OPCs, Microglia]
- % Change values here — everything downstream adapts automatically
- Klist = [1, 2, 1, 1];
- % Cell type names (must match order of Klist)
- cellTypeNames = {'Astrocytes', 'Neurons', 'OPCs', 'Microglia'};
- % Groups to process
- groups = {'1week', '6week' };
- allDatasets = {datasets_1week, datasets_6week};
- allGenes = {genes_1week, genes_6week };
- % --- End Configuration ---
- % Make profile names automatically from Klist and cellTypeNames
- % e.g. Klist=[1,2,1,1] -> {'Astrocyte','Neuron 1','Neuron 2','OPC','Microglia'}
- profileNames = {};
- for ct = 1:length(Klist)
- baseName = cellTypeNames{ct};
- % Remove trailing 's' for singular form (e.g. 'Astrocytes' -> 'Astrocyte')
- if baseName(end) == 's'
- baseName = baseName(1:end-1);
- end
- if Klist(ct) == 1
- profileNames{end+1} = baseName;
- else
- for f = 1:Klist(ct)
- profileNames{end+1} = [baseName, ' ', num2str(f)];
- end
- end
- end
- nFactors = sum(Klist); % Total NMF factors across all cell types
- % Map each factor index back to its cell type (used for gene labels in plots)
- % e.g. Klist=[1,2,1,1] -> factorCellTypeIdx = [1, 2, 2, 3, 4]
- factorCellTypeIdx = [];
- for ct = 1:length(Klist)
- factorCellTypeIdx = [factorCellTypeIdx, repmat(ct, 1, Klist(ct))];
- end
- % --- Main Loop: one iteration per group (1week, 6week) ---
- for g = 1:length(groups)
- groupName = groups{g};
- current_datasets = allDatasets{g};
- current_genes = allGenes{g};
- disp(['=== Starting Joint Analysis for Group: ', groupName, ' ===']);
- % Create output directory
- outputDir = fullfile(sampleDir, ['Joint_Analysis_', groupName]);
- if ~exist(outputDir, 'dir')
- mkdir(outputDir);
- end
- disp('Step 1: Pooling data from all samples...');
- pooled_Y = cell(1, length(Klist));
- pooled_R_vec = []; % Reactivity gene counts: [TotalSpots x nReactivityGenes]
- spot_origin = []; % Tracks which sample each spot came from
- for k = 1:length(current_datasets)
- fdir = current_datasets{k};
- mat_file = fullfile(sampleDir, fdir, [fdir, '_normalized.mat']);
- if ~exist(mat_file, 'file')
- disp([' Skipping ', fdir, ' (file not found)']);
- continue;
- end
- fprintf(' Loading %s... ', fdir);
- load(mat_file, 'S');
- C = readCelltypeGeneCSV(1);
- C = array2geneCounts(C, S);
- R = struct;
- R.names = current_genes;
- R = array2geneCounts(R, S);
- for ct = 1:length(Klist)
- if k == 1
- pooled_Y{ct} = C.vec(:, :, ct);
- else
- pooled_Y{ct} = [pooled_Y{ct}; C.vec(:, :, ct)];
- end
- end
- pooled_R_vec = [pooled_R_vec; R.vec];
- num_spots = size(C.vec, 1);
- spot_origin = [spot_origin; repmat({fdir}, num_spots, 1)];
- fprintf('Done. (%d spots added)\n', num_spots);
- clear S C R
- end
- disp('Step 2: Running joint NMF models...');
- C_ref = readCelltypeGeneCSV(1);
- U_joint = cell(1, length(Klist)); % Spatial loadings per cell type
- V_joint = cell(1, length(Klist)); % Gene profiles per cell type
- U_total_matrix = []; % All factors concatenated: [TotalSpots x nFactors]
- for ct = 1:length(Klist)
- disp([' Processing cell type: ', cellTypeNames{ct}]);
- Y = pooled_Y{ct};
- K = Klist(ct);
- nruns = 500;
- niters = 1000;
- rho = 1e2;
- flag = [0, 0];
- [U, V] = RINMF(Y, K, nruns, niters, rho, flag);
- % Round U if binary flag is set
- if isequal(flag, [1, 0])
- U = round(U);
- end
- U_joint{ct} = U;
- V_joint{ct} = V;
- U_total_matrix = [U_total_matrix, U];
- for k_nmf = 1:K
- h_profile = figure('Visible', 'off', 'Position', [100, 100, 800, 1000]);
- barh(V(:, k_nmf))
- xlabel('Gene Contribution (Global)')
- set(gca, 'YDir', 'reverse')
- set(gca, 'YTick', 1:40);
- ct_idx = factorCellTypeIdx(sum(Klist(1:ct-1)) + k_nmf);
- try
- set(gca, 'YTickLabel', C_ref.names(:, ct_idx));
- catch
- disp(' Warning: Could not set gene labels.');
- end
- title({['Global Joint Factor ', num2str(k_nmf)], ...
- [cellTypeNames{ct}, ' (', groupName, ')']});
- fname = sprintf('Joint_Profile_%s_%s_Factor%d.png', groupName, cellTypeNames{ct}, k_nmf);
- saveas(h_profile, fullfile(outputDir, fname));
- close(h_profile);
- end
- end
- clear ct k_nmf
- disp('Step 4: Calculating joint statistics (Pearson & Cosine)...');
- numSamples = 10^5; % Random permutations for cosine similarity p-value
- temp = zeros(nFactors, length(current_genes));
- pearson_r_table = array2table(temp, 'RowNames', profileNames, 'VariableNames', current_genes);
- pearson_p_table = array2table(temp, 'RowNames', profileNames, 'VariableNames', current_genes);
- cosine_theta_table = array2table(temp, 'RowNames', profileNames, 'VariableNames', current_genes);
- cosine_p_table = array2table(temp, 'RowNames', profileNames, 'VariableNames', current_genes);
- for mr = 1:length(current_genes)
- for mct = 1:nFactors
- % Pearson: sqrt transform
- R_vec_pearson = sqrt(pooled_R_vec(:, mr));
- U_vec_pearson = sqrt(U_total_matrix(:, mct));
- % Cosine: raw counts (no transform )
- R_vec_cosine = pooled_R_vec(:, mr);
- U_vec_cosine = U_total_matrix(:, mct);
- min_len = min(length(R_vec_pearson), length(U_vec_pearson));
- R_vec_pearson = R_vec_pearson(1:min_len);
- U_vec_pearson = U_vec_pearson(1:min_len);
- R_vec_cosine = R_vec_cosine(1:min_len);
- U_vec_cosine = U_vec_cosine(1:min_len);
- % Pearson correlation
- [r, p] = corrcoef(R_vec_pearson, U_vec_pearson);
- pearson_r_table{mct, mr} = r(1, 2);
- pearson_p_table{mct, mr} = p(1, 2);
- % Cosine similarity with empirical p-value
- [cos_r, cos_p, ~] = getcostheta(R_vec_cosine, U_vec_cosine, numSamples);
- cosine_theta_table{mct, mr} = cos_r;
- cosine_p_table{mct, mr} = cos_p;
- end
- end
- clear mr mct
- pearson_r_table.Properties.VariableNames = strcat('Pearson_r_', pearson_r_table.Properties.VariableNames);
- pearson_p_table.Properties.VariableNames = strcat('Pearson_p_', pearson_p_table.Properties.VariableNames);
- cosine_theta_table.Properties.VariableNames = strcat('Cosine_theta_', cosine_theta_table.Properties.VariableNames);
- cosine_p_table.Properties.VariableNames = strcat('Cosine_p_', cosine_p_table.Properties.VariableNames);
- combined_joint_table = [pearson_r_table, pearson_p_table, cosine_theta_table, cosine_p_table];
- csvName = fullfile(outputDir, ['Joint_Stats_', groupName, '.csv']);
- writetable(combined_joint_table, csvName, 'WriteRowNames', true);
- disp([' Saved joint statistics to: ', csvName]);
- disp('Step 5: Saving joint results...');
- saveFile = fullfile(outputDir, ['Joint_Results_', groupName, '.mat']);
- save(saveFile, 'U_joint', 'V_joint', 'pooled_Y', 'spot_origin', 'cellTypeNames', 'profileNames', 'combined_joint_table');
- disp([' Saved joint MAT file to: ', saveFile]);
- disp(['=== Finished Joint Analysis for ', groupName, ' ===']);
- disp(' ');
- end
- clear g
- disp('All joint analyses completed.');
coreJointNMF.m at commit 124a09e, no license · at the source
Overview
- Department of Biomedical Engineering, Michigan State University, East Lansing, MI, United States
- Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, United States
- Department of Electrical and Computer Engineering, Michigan State University, East Lansing, MI, United States
Abstract
The foreign body reaction to implanted electrodes in the brain has long been recognized as a major challenge impacting the performance and reliability of indwelling neurotechnologies. Spatially resolved transcriptomic approaches have enabled high-resolution mapping of cellular and molecular dynamics at the device-tissue interface, yielding novel insight into both acute and chronic tissue responses. Recent whole-transcriptome profiling methods generate exceptionally dense gene expression datasets from individual samples, offering unprecedented resolution and analytical power. Yet, limited studies have explored aggregated results from larger datasets and sample-to-sample variation within an implanted cohort using such techniques due to high costs and complicated downstream analyses. In this work, we provide a comprehensive report of spatial transcriptomics data collected from an expanded cohort of rats (n = 14 rats) implanted with silicon microelectrode arrays in the motor cortices for 1 week (acute) and 6 weeks (chronic). This larger dataset enabled us to explore the variation in results across samples, assess outliers, and examine potential batch effects. We employed differential expression analysis to identify top differentially expressed genes (DEGs) in spatially defined regions at the device-tissue interface to reveal novel biomarkers in the aggregated dataset. We assessed sample-to-sample variabilities, and applied a factorization strategy to identify prominent cell-type contributors of the top DEGs. Using network-based co-expression analysis, we identified gene modules, hub genes, and central regulatory processes governing the device-tissue interface. Our results show: (a) greater variation of top DEGs across samples at the 1-week time point with notable microglial and astroglial cell-type contributors, (b) lower variation of top DEGs across samples and a shift to prominent astroglial cell-type contributors at the 6-week time point, and (c) novel biomarkers that suggest major macrophage- and microglial mediated processes and homeostasis events at the 1-week time point, and greater tissue remodeling, apoptotic and synaptic changes at the 6-week time point. These findings support previous ideas on the evolving tissue response to implanted devices, and present novel details on biomarkers, biological processes and sample variation. Additionally, this study provides a framework for assessing larger datasets employing high-dimensional spatial transcriptomics and highlight key considerations related to across-sample variability and batch effects.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above, with 4 matches between paragraphs and lines of code.
msureil/SpatioBiomarker
124a09e7efa76b2167cda2c4cda091186bf16625, 13 March 2026Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
14 files
- ALS_NMF.m, MATLAB, 34 lines
- MU_NMF.m, MATLAB, 33 lines
- RINMF.m, MATLAB, 74 lines
- array2geneCounts.m, MATLAB, 14 lines
- coreJointNMF.m, MATLAB, 250 lines, 2 matches
- coreNMF.m, MATLAB, 378 lines, 2 matches
- geneCounts.m, MATLAB, 15 lines
- getcostheta.m, MATLAB, 33 lines
- pvalfromsim.m, MATLAB, 29 lines
- readCelltypeGeneCSV.m, MATLAB, 14 lines
- readSampleData.m, MATLAB, 128 lines
- stplot.m, MATLAB, 18 lines
- stvplot.m, MATLAB, 24 lines
- README.md, Text, 16 lines
The paper's code and data availability statement is in the Data section.
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- 4 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
Datasets cited
- bioproject:PRJNA1089183, at NCBI BioProject; found in “Data availability statement”
Other data links
- ncbi.nlm.nih.gov/
bioproject/ , NCBI; found in “Data availability statement”1472787
Data availability statement
The data used in this study are publicly available at the following URLs. Previously reported (1 week sample B, 1 week sample C, 6 week sample B and 6 week sample C) can be found at www.ncbi.nlm.nih.gov/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, pages, dates, 6 authors, 7 keywords, 118 references.
Cite
This paper
Gupta, B., Chakraborty, A., Saxena, A., Moore, M. G., Whitsitt, Q. A., & Purcell, E. K. (2026). Spatial transcriptomics on an expanded dataset at the brain-electrode interface: exploration of variability and identification of novel biomarkers. Frontiers in neuroscience, 20, 1852774. https://
BibTeX
@article{gupta2026spatia
author = {Gupta, Bhavna and Chakraborty, Anirban and Saxena, Akash and Moore, Michael G and Whitsitt, Quentin A and Purcell, Erin K},
title = {{Spatial transcriptomics on an expanded dataset at the brain-electrode interface: exploration of variability and identification of novel biomarkers}},
journal = {Frontiers in neuroscience},
year = {2026},
month = jun,
volume = {20},
pages = {1852774},
publisher = {Frontiers Media SA},
issn = {1662-4548},
doi = {10.3389/
url = {https://
pmid = {42375631},
pmcid = {PMC13311015}
}
RIS
TY - JOUR
AU - Gupta, Bhavna
AU - Chakraborty, Anirban
AU - Saxena, Akash
AU - Moore, Michael G
AU - Whitsitt, Quentin A
AU - Purcell, Erin K
TI - Spatial transcriptomics on an expanded dataset at the brain-electrode interface: exploration of variability and identification of novel biomarkers
T2 - Frontiers in neuroscience
J2 - Front Neurosci
PY - 2026
DA - 2026/
VL - 20
SP - 1852774
SN - 1662-4548
PB - Frontiers Media SA
DO - 10.3389/
UR - https://
LA - en
ER -
CSL-JSON
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