Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model.
The 8 matches
- [1] § MATERIALS AND METHODS › Determining biological enrichment of tissue remodeling and the immune system during TBI using RNA expression data ↔ 4_functionalEnrichmentAnalysis.py, lines 66 to 114 · score 0.85 · GO_Biological_Process_2021, GO_Cellular_Component_2025, functional enrichment, GO terms, cutoff, enrichr · Report a mismatch
- [2] § MATERIALS AND METHODS › Differential gene expression analysis ↔ 2_edgeR_differentialGeneExpression.R, lines 82 to 120 · score 0.68 · quasi likelihood, QL, gene expression, cutoff, batch, log2 · Report a mismatch
- [3] § RESULTS › Different sex hormones are correlated with similar immune responses in male and female mice ↔ 5a_SemanticSimilarity_Immune.R, lines 1 to 59 · score 0.66 · innate immune, immune processes, enriched GO, BP terms, biological processes, semantic · Report a mismatch
- [4] § RESULTS › Characterizing the early innate immune response to cortical injury ↔ 5a_SemanticSimilarity_Immune.R, lines 1 to 59 · score 0.62 · innate immune processes, functionally enriched GO, BP terms, Biological Process, semantic, DEGs · Report a mismatch
- [5] § MATERIALS AND METHODS › Correlating cortical gene expression with steroid hormones using differentially expressed eigengenes ↔ 3_normalizeRNAseqData.R, lines 45 to 106 · score 0.60 · DESeq2, contralateral sample, vst, Batch, ipsilateral, mouse · Report a mismatch
- [6] § RESULTS › Characterization of tissue remodeling biological processes and cellular components after TBI ↔ 5b_SemanticSimilarity_TissueRemodeling.R, lines 60 to 111 · score 0.60 · tissue remodeling biological, Cellular Components, BP term, matrix, semantic, CC · Report a mismatch
- [7] § MATERIALS AND METHODS › Experimental design and statistical analysis ↔ 4_functionalEnrichmentAnalysis.py, lines 66 to 114 · score 0.57 · Functional enrichment, GO terms, Enrichr, overlap, scores, FDR · Report a mismatch
- [8] § MATERIALS AND METHODS › Determining biological enrichment of tissue remodeling and the immune system during TBI using RNA expression data ↔ 5b_SemanticSimilarity_TissueRemodeling.R, lines 1 to 58 · score 0.56 · tissue remodeling, enriched GO, cellular component, score, semantic, immune · Report a mismatch
Paper
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The authors' code
Python · 138 lines · 8.5 KB · Apache-2.0 · 2 matches
- ###############################################################
- ## 4_functionalEnrichmentAnalysis.py ##
- ## ______ ______ __ __ ##
- ## /\ __ \ /\ ___\ /\ \/\ \ ##
- ## \ \ __ \ \ \___ \ \ \ \_\ \ ##
- ## \ \_\ \_\ \/\_____\ \ \_____\ ##
- ## \/_/\/_/ \/_____/ \/_____/ ##
- ## @Developed by: Stabenfeldt and Plaisier Labs ##
- ## (https://plaisierlab.engineering.asu.edu/) ##
- ## Arizona State University ##
- ## 242 ISTB1, 550 E Orange St ##
- ## Tempe, AZ 85281 ##
- ## @github: https://github.com/plaisier-lab/sex_specific_tbi ##
- ## @Author: Amberlyn Simmons, Sierra Wilferd ##
- ## @License: <> ##
- ## ##
- ## If this program is used in your analysis please ##
- ## mention who built it. Thanks. :-) ##
- ###############################################################
- ## Purpose: to identify functionally enriched gene ontology biological process and cellular component terms from differentially expressed RNAseq data.
- #############
- ## imports ##
- #############
- import numpy as np
- import pandas as pd
- from sklearn.decomposition import PCA
- from scipy import stats
- from scipy.stats import pearsonr
- from statsmodels.stats.multitest import multipletests
- import gseapy as gp
- ## used to convert ensembl IDs to gene IDs
- import mygene
- mg = mygene.MyGeneInfo()
- import seaborn as sns
- from matplotlib.backends.backend_pdf import PdfPages
- import matplotlib.pyplot as plt
- import matplotlib as mpl
- ##################
- ## Declare data ##
- ##################
- ## SW DEGs
- filepath1 = '../Data/2b_Final_DEGs_SW/DEGs/'
- conditions1 = ['injured24_female', 'injured72_female', 'injured24_male', 'injured72_male']
- addNaive = ['naive_male_upregulated', 'naive_male_downregulated', 'naive_female_upregulated', 'naive_female_downregulated']
- date = '07012025'
- saveOut1 = '../Data/4_FunctionalEnrichmentAnalysis/FEAresults_SW/'
- ####################################
- ## Functional Enrichment Analysis ##
- ####################################
- # merge dictionaries
- build_translator_BP = pd.DataFrame(columns = ['Human readable'])
- build_translator_CC = pd.DataFrame(columns = ['Human readable'])
- # set up enrichment - USE MOUSE!!!!
- countDEG = pd.DataFrame(columns = [i + '_upregulated' for i in conditions1] + [i + '_downregulated' for i in conditions1], index = ['HowMany', 'Direction'])
- overlapDEG = pd.DataFrame(columns = [i + '_upregulated' for i in conditions1] + [i + '_downregulated' for i in conditions1], index = ['HowMany', 'Direction'])
- for naive in addNaive:
- countDEG.loc['HowMany', naive] = int(0)
- overlapDEG.loc['HowMany', naive] = int(0)
- #countDEG.loc['Direction', naive] = naive.split('_')[2]
- for condition1 in conditions1:
- print(condition1)
- allDEGs = pd.read_csv(filepath1 + condition1 + '_DEGlist_symb_' + date + '.csv', index_col = 0)
- # significant genes
- upDEGs = allDEGs.loc[[i for i in allDEGs.index if allDEGs.loc[i, 'logFC'] >= 1 and allDEGs.loc[i, 'FDR'] <= 0.1]]
- downDEGs = allDEGs.loc[[i for i in allDEGs.index if allDEGs.loc[i, 'logFC'] <= -1 and allDEGs.loc[i, 'FDR'] <= 0.1]]
- # save out how many DEGs there are
- countDEG.loc['HowMany', condition1 + '_upregulated'] = len(upDEGs.index)
- countDEG.loc['HowMany', condition1 + '_downregulated'] = len(downDEGs.index)
- countDEG.loc['Direction', condition1 + '_upregulated'] = 'upregulated'
- countDEG.loc['Direction', condition1 + '_downregulated'] = 'downregulated'
- # Less code in a for loop
- dictDEGs = {'upregulated': upDEGs, 'downregulated':downDEGs}
- for direction1 in dictDEGs.keys():
- # Translate
- mapped = list(mg.querymany(list(dictDEGs[direction1].index), scopes='ensembl.gene', species=10090, as_dataframe=True)['symbol'].dropna())
- # Run enrichment
- enrichment_BP = gp.enrichr(gene_list=mapped, gene_sets=['GO_Biological_Process_2021'], organism='Mouse', outdir= saveOut1 + condition1 + '_' + direction1 + '_FEA_BP', cutoff=0.05, no_plot=True)
- enrichment_CC = gp.enrichr(gene_list=mapped, gene_sets=['GO_Cellular_Component_2025'], organism='Mouse', outdir= saveOut1 + condition1 + '_' + direction1 + '_FEA_CC', cutoff=0.05, no_plot=True)
- # Make the overlap not a date in excel
- enrichment_BP.results['DEGs'] = [i.split('/')[0] for i in enrichment_BP.results['Overlap']]
- enrichment_BP.results['GO genes'] = [i.split('/')[1] for i in enrichment_BP.results['Overlap']]
- enrichment_BP.results['Overlap'] = [float(i.split('/')[0])/float(i.split('/')[1]) for i in enrichment_BP.results['Overlap']]
- enrichment_CC.results['DEGs'] = [i.split('/')[0] for i in enrichment_CC.results['Overlap']]
- enrichment_CC.results['GO genes'] = [i.split('/')[1] for i in enrichment_CC.results['Overlap']]
- enrichment_CC.results['Overlap'] = [float(i.split('/')[0])/float(i.split('/')[1]) for i in enrichment_CC.results['Overlap']]
- # reorder
- enrichment_BP.results = enrichment_BP.results[['Gene_set', 'Term', 'DEGs', 'GO genes', 'Overlap', 'P-value', 'Adjusted P-value', 'Old P-value', 'Old Adjusted P-value', 'Odds Ratio', 'Combined Score', 'Genes']]
- enrichment_CC.results = enrichment_CC.results[['Gene_set', 'Term', 'DEGs', 'GO genes', 'Overlap', 'P-value', 'Adjusted P-value', 'Old P-value', 'Old Adjusted P-value', 'Odds Ratio', 'Combined Score', 'Genes']]
- # Save out data
- enrichment_BP.results.to_csv(saveOut1 + 'enrichr_results/BP_' + condition1 + '_' + direction1 + '.csv')
- enrichment_CC.results.to_csv(saveOut1 + 'enrichr_results/CC_' + condition1 + '_' + direction1 + '.csv')
- # calculate overlap
- # identify significant results
- enrichment_BP.results.loc[enrichment_BP.results['Adjusted P-value']<=0.05].loc[enrichment_BP.results['Overlap'] >= 0.1].to_csv(saveOut1 + 'enrichr_results/allData_significantGOterms_BP_' + condition1 + '_' + direction1 + '.csv')
- enrichment_CC.results.loc[enrichment_CC.results['Adjusted P-value']<=0.05].loc[enrichment_CC.results['Overlap'] >= 0.1].to_csv(saveOut1 + 'enrichr_results/allData_significantGOterms_CC_' + condition1 + '_' + direction1 + '.csv')
- #break
- # pull out terms only
- pd.DataFrame(set(['GO:' + i.split('(GO:')[1].rstrip(')') for i in enrichment_BP.results.loc[enrichment_BP.results['Adjusted P-value']<=0.05].loc[enrichment_BP.results['Overlap'] >= 0.1, 'Term'] if 'GO:' in i]), columns = ['GO terms']).to_csv(saveOut1 + 'enrichr_results/significantGOterms_BP_' + condition1 + '_' + direction1 + '.csv')
- pd.DataFrame(set(['GO:' + i.split('(GO:')[1].rstrip(')') for i in enrichment_CC.results.loc[enrichment_CC.results['Adjusted P-value']<=0.05].loc[enrichment_CC.results['Overlap'] >= 0.1, 'Term'] if 'GO:' in i]), columns = ['Term']).to_csv(saveOut1 + 'enrichr_results/significantGOterms_CC_' + condition1 + '_' + direction1 + '.csv')
- # build translators of GO terms -- combine with currated terms
- for term1 in enrichment_BP.results['Term']:
- goTerm = term1.split('(')[1].rstrip(')')
- humanReadable_BP = term1.split('(')[0].rstrip(' ')
- build_translator_BP.loc[goTerm,'Human readable'] = humanReadable_BP
- for term1 in enrichment_CC.results['Term']:
- goTerm = term1.split('(')[1].rstrip(')')
- humanReadable_CC = term1.split('(')[0].rstrip(' ')
- build_translator_CC.loc[goTerm,'Human readable'] = humanReadable_CC
- # save out translators
- build_translator_BP.to_csv(saveOut1 + 'enrichr_results/translator/GOBP_translator_fromRNAdata.csv', sep=',')
- build_translator_CC.to_csv(saveOut1 + 'enrichr_results/translator/GOCC_translator_fromRNAdata.csv', sep=',')
- ###################
- ## make barplots ##
- ###################
- pp2 = PdfPages(saveOut1 + 'Figures/Figures_DEGcounts.pdf')
- plt.title('DEGs in each condition')
- ax = sns.barplot(countDEG.T, x = countDEG.columns, y = 'HowMany', hue = 'Direction')
- plt.tick_params(axis='x', labelrotation=90)
- for container in ax.containers:
- ax.bar_label(container)
- plt.tight_layout()
- #sns.catplot(countDEG.T, kind="bar", x=countDEG.columns, y = 'HowMany', col = 'Direction', height=4, aspect=.5)
- pp2.savefig()
- plt.clf()
- pp2.close()
- plt.close()
- # fin
4_functionalEnrichmentAnalysis.py at commit e1319d6, under Apache-2.0 · at the source
Overview
- School of Biological and Health Systems Engineering, Arizona State University, Tempe, AZ, USA
- Psychology, School of Life Sciences, Arizona State University, Tempe, AZ, USA
- Neuroscience, School of Life Sciences, ASU, Tempe, AZ, USA
- Department of Neurological Surgery, UMass Chan Medical School, Worcester, MA, USA
- John Shufeldt School of Medicine and Medical Engineering, ASU, Tempe, AZ, USA
Abstract
Accumulating evidence supports sex differences in traumatic brain injury (TBI) outcomes. However, the underlying processes that lead to sex differences are not well understood. TBI results in the initiation of molecular and cellular responses that facilitate the progression of neurodegeneration. Little is known about how the circulating hormone profile is altered in response to TBI and whether sex differences in endocrine responses might shape secondary injury pathologies. Using intact male and female mice in a preclinical TBI model, we assessed changes in plasma hormone concentrations and cortical gene expression at 24 and 72 hours after TBI. We demonstrate that males and females exhibit sex-specific alterations in circulating levels of testosterone, androstenedione, estradiol, and dehydroepiandrosterone (DHEA) in response to TBI. We also identified sex differences in the expression of genes that are involved in immune responses and tissue remodeling after injury. Moreover, we report divergent circulating hormone and gene expression correlations between sexes.
Reproduced under the paper's license (CC BY-NC), from the paper cited above.
Repositories
Its files are read in the Code ↔ Paper reader above, with 8 matches between paragraphs and lines of code.
Zenodo 21726001
Availability: 1 check, the latest on 25 October 2026: the link answers (HTTP 200)
- 25 October 2026: the link answers (HTTP 200)
15 files
- 1a_run_allScripts.sh, Shell, 32 lines
- 1b_run_allR.R, R, 25 lines
- 2_edgeR_differentialGene
Expression.R , R, 186 lines - 3_normalizeRNAseqData.R, R, 192 lines
- 4_functionalEnrichmentAn
alysis.py , Python, 138 lines - 4a_functionalEnrichmentA
nalysis_VennDiagrams.R , R, 84 lines - 5_semanticSimilarity.R, R, 230 lines
- 5a_SemanticSimilarity_Im
mune.R , R, 257 lines - 5b_SemanticSimilarity_Ti
ssueRemodeling.R , R, 438 lines - 6_Eigengenes.py, Python, 200 lines
- 7_HormoneCorrelation.py, Python, 130 lines
- 8_Eigengene_Hormone_Scat
terplots.R , R, 225 lines - 9_plot_CorrelationTables
.py , Python, 141 lines - LICENSE, License, 201 lines
- README.md, Text, 2 lines
plaisier-lab/sex_specific_tbi
e1319d67d1da18e92598a66689d1ff8473f512ed, 30 July 2026Availability: 1 check, the latest on 25 October 2026: the link answers
- 25 October 2026: the link answers
15 files
- 1a_run_allScripts.sh, Shell, 32 lines
- 1b_run_allR.R, R, 25 lines
- 2_edgeR_differentialGene
Expression.R , R, 186 lines, 1 match - 3_normalizeRNAseqData.R, R, 192 lines, 1 match
- 4_functionalEnrichmentAn
alysis.py , Python, 138 lines, 2 matches - 4a_functionalEnrichmentA
nalysis_VennDiagrams.R , R, 84 lines - 5_semanticSimilarity.R, R, 230 lines
- 5a_SemanticSimilarity_Im
mune.R , R, 257 lines, 2 matches - 5b_SemanticSimilarity_Ti
ssueRemodeling.R , R, 438 lines, 2 matches - 6_Eigengenes.py, Python, 200 lines
- 7_HormoneCorrelation.py, Python, 130 lines
- 8_Eigengene_Hormone_Scat
terplots.R , R, 225 lines - 9_plot_CorrelationTables
.py , Python, 141 lines - LICENSE, License, 201 lines
- README.md, Text, 2 lines
The paper's code and data availability statement is in the Data section.
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Data
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Reproduced under the paper's license (CC BY-NC), from the paper cited above.
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Version 1, 25 October 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 12 MeSH terms, 4 funders, 63 references.
Cite
This paper
Simmons, A., Wilferd, S. F., Campagnuolo, S., Pena, V., Bimonte-Nelson, H., Newbern, J., Sirianni, R. W., Plaisier, C. L., & Stabenfeldt, S. E. (2026). Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model. Science advances, 12(43), eaei5171. https://
BibTeX
@article{simmons2026diff
author = {Simmons, Amberlyn and Wilferd, Sierra F and Campagnuolo, Sofia and Pena, Veronica and Bimonte-Nelson, Heather and Newbern, Jason and Sirianni, Rachael W and Plaisier, Christopher L and Stabenfeldt, Sarah E},
title = {{Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model}},
journal = {Science advances},
year = {2026},
month = oct,
volume = {12},
number = {43},
pages = {eaei5171},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/
url = {https://
pmid = {42905827},
pmcid = {PMC13685967}
}
RIS
TY - JOUR
AU - Simmons, Amberlyn
AU - Wilferd, Sierra F
AU - Campagnuolo, Sofia
AU - Pena, Veronica
AU - Bimonte-Nelson, Heather
AU - Newbern, Jason
AU - Sirianni, Rachael W
AU - Plaisier, Christopher L
AU - Stabenfeldt, Sarah E
TI - Differential sex-dependent responses of circulating steroid hormones and cortical gene expression in a traumatic brain injury model
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/
VL - 12
IS - 43
SP - eaei5171
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/
UR - https://
LA - en
ER -
CSL-JSON
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