Exploring the molecular underpinnings of neuropathic pain in primary afferent subtypes

Barry, A. M. (2022). Exploring the molecular underpinnings of neuropathic pain in primary afferent subtypes [PhD thesis]. University of Oxford. ORA

Data is also availale from Barry (2022) (PhD Thesis), GSE216444 and processed results can be queried on our database (DRG Directory).

Supplementary tables

DOI

Allison Marie Barry
Green Templeton College
University of Oxford
allimariebarry@gmail.com

DRG subtype study (Ch2-Ch4)

Please cite our paper in PAIN for data tables used from these chapters.

Naive comparisions

~ Population
~ Population + Sex
  • DRGsubtype_Zheng2019-genesets.csv : 8 neuronal subtype genesets curated from Zheng et al 2019 (DOI: 10.1016/j.neuron.2019.05.039) GSE131230
  • DRGsubtype_geneenrichment.csv : Gene enrichment for each subtype in the current study, based on 75% confidence intervals
  • DRGsubtype_sex_DEG.xlsx : Differentially expressed genes (DEGs) for each subtype, with female reference
  • DRGsubtype_sex_DEGoverlap.csv : Overlap in DEGs across subtype
  • DRGsubtype_sex_GO.xlsx : GO term analyses using GoSeq (R) for each subtype
  • DRGsubtype_sex_GSEA.xlsx : GSEA analyses using ClusterProfiler (R) against all gene sets available from the Molecular Signatures Database (MSigDB). Samples were ranked by LFC.

General Injury signatures

~ Time_Condition #grouping factor
  • DRGsubtype_general-injury_DEG: 3D tab: Ipsilateral vs contralateral samples from 3 days post-SNI (an acute timepoint). 4W tab: Ipsilateral vs contralateral samples from 4 days post-SNI (a chronic timepoint). 4W v 3D tab: Comparison of ipsilateral samples across timepoints.Contains samples from all subtypes. P < 0.05, all LFC.
  • DRGsubtype_general-injury_DEGoverlap: overlapping DEGs (LFC>1, padj<0.05) between general 3D and 4W analyses.
  • DRGsubtype_gneeral-injury_GSEA: GSEA analyses using ClusterProfiler (R) against all gene sets available from the Molecular Signatures Database (MSigDB). Samples were ranked by LFC.
  • DRGsubtype_general-injury_GO: GO term analyses using GoSeq (R) for general comparisons

Subtype Injury signatures

~ Time_Condition_Population #grouping factor
  • DRGsubtype_subtype-injury_opposingDEGs_3D : DEG list (LFC>1, padj<0.05) which are regulated in opposing directions across subtype (+1 = up, -1 = down).
  • DRGsubtype_subtype-injury_GO : GO term analyses using GoSeq (R) for each subtype.
  • DRGsubtype_subtype-injury_DEG: 3D tabs: Ipsilateral vs contralateral samples from 3 days post-SNI (an acute timepoint). 4W tabs: Ipsilateral vs contralateral samples from 4 days post-SNI (a chronic timepoint). Contains samples from all subtypes. P < 0.05, all LFC.

Sexual Dimorphism

#Populations subsetted
~ Time_Condition*Sex #interaction model
~ Time_Condition + Sex #additive 

Additive model contrasts M vs F with 4W_ispilateral vs 4W_contralateral

  • DRGsubtype_subtype-injury_sexdimorphism_DEG

Injured and Intact afferents (Ch5, Atf3)

Otherwise unpublished, please cite this thesis for data used from this chapter.

Injury comparisions

~ Time_Condition
  • ATF3_injury_DEGs: DEGs for 3D or 4W post-SNI.
  • ATF3_generegulation_DEGs / transcriptionfactors / generalimmune: Subsets of ATF3_injury_DEGs based on biological/molecular function
  • ATF3_injury_GSEA-hallmark : GSEA analyses using ClusterProfiler (R) against hallmark gene sets available from the Molecular Signatures Database (MSigDB). Samples were ranked by LFC.

Sex interaction

~ Time_Condition*Sex
  • ATF3_sex_DEGs : DEGs for 3D or 4W post-SNI. Contralateral + Female baseline. Injured vs contralateral (injured) and intact vs contralateral (intact) comparisions.
  • ATF3_sex_GO : GO term analyses using GoSeq (R) for 3D intact.