Pathway-targeting gene matrix for Drosophila gene set enrichment analysis

Cheng, Jack; Hsu, Lee-Fen; Liu, Hsin-Ping; Lin, Wei-Yong

doi:10.1371/journal.pone.0259201

Cited by 6 publications

(4 citation statements)

References 23 publications

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“…Standard data processing and calculation of DE revealed 98 DEGs ( p adj ≤ 0.05). We note that this number is too low for gene ontology (GO) or similar analyses [ 78 , 79 ] (data not shown) and that gene set enrichment analysis (GSEA) is not readily available for Drosophila [ 80 ]. Importantly, the number of genes we identified is comparable to the number of changes in ribosome-loaded transcripts observed in specific mouse cell types after SSRI treatment, including serotonergic neurons of the raphe nucleus [ 77 ] and S100a10 corticostriatal neurons [ 21 ], and the lower range (48–1243 DEGs) of an additional 27 brain regions recently analyzed in mice [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Bonanno

Krantz

2023

Transl Psychiatry

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The transcriptional effects of SSRIs and other serotonergic drugs remain unclear, in part due to the heterogeneity of postsynaptic cells, which may respond differently to changes in serotonergic signaling. Relatively simple model systems such as Drosophila afford more tractable microcircuits in which to investigate these changes in specific cell types. Here, we focus on the mushroom body, an insect brain structure heavily innervated by serotonin and comprised of multiple different but related subtypes of Kenyon cells. We use fluorescence-activated cell sorting of Kenyon cells, followed by either bulk or single-cell RNA sequencing to explore the transcriptomic response of these cells to SERT inhibition. We compared the effects of two different Drosophila Serotonin Transporter (dSERT) mutant alleles as well as feeding the SSRI citalopram to adult flies. We find that the genetic architecture associated with one of the mutants contributed to significant artefactual changes in expression. Comparison of differential expression caused by loss of SERT during development versus aged, adult flies, suggests that changes in serotonergic signaling may have relatively stronger effects during development, consistent with behavioral studies in mice. Overall, our experiments revealed limited transcriptomic changes in Kenyon cells, but suggest that different subtypes may respond differently to SERT loss-of-function. Further work exploring the effects of SERT loss-of-function in other circuits may be used help to elucidate how SSRIs differentially affect a variety of different neuronal subtypes both during development and in adults.

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Section: Discussionmentioning

confidence: 99%

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Bonanno

Krantz

2023

Transl Psychiatry

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“…Gene set enrichment analysis was run using the GSEA software v. 4.2.3 [ 27 ]. Drosophila -specific gene matrices for both KEGG and Reactome-based GSEA aliases were taken from [ 47 ]. TMM-normalized TPMs were extracted from EdgeR analysis and used as input for two-condition comparisons using GSEA software.…”

Section: Methodsmentioning

confidence: 99%

Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance

Cabrera,

Hoard,

Gibson

et al. 2023

PLoS Pathog

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Innate immune priming increases an organism’s survival of a second infection after an initial, non-lethal infection. We used Drosophila melanogaster and an insect-derived strain of Enterococcus faecalis to study transcriptional control of priming. In contrast to other pathogens, the enhanced survival in primed animals does not correlate with decreased E. faecalis load. Further analysis shows that primed organisms tolerate, rather than resist infection. Using RNA-seq of immune tissues, we found many genes were upregulated in only primed flies, suggesting a distinct transcriptional program in response to initial and secondary infections. In contrast, few genes continuously express throughout the experiment or more efficiently re-activate upon reinfection. Priming experiments in immune deficient mutants revealed Imd is largely dispensable for responding to a single infection but needed to fully prime. Together, this indicates the fly’s innate immune response is plastic—differing in immune strategy, transcriptional program, and pathway use depending on infection history.

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“…Standard data processing and calculation of DE revealed 98 DEGs (padj £ 0.05). We note that this number is too low for gene ontology (GO) or similar analyses available for Drosophila [74,75] (data not shown) and that gene set enrichment analysis (GSEA) is not readily available for Drosophila [76]. Importantly, the number of genes we identified is comparable to the number of changes in ribosome-loaded transcripts observed in specific mouse cell types after SSRI treatment, including serotonergic neurons of the raphe nucleus [73], S100a10 corticostriatal neurons [21] and the lower range (48-1243 DEGs) of an additional 27 brain regions recently analyzed in mice [14].…”

Section: Bulk Rna-seqmentioning

confidence: 99%

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Krantz

Bonanno

2023

Preprint

View full text Add to dashboard Cite

The transcriptional effects of SSRIs and other serotonergic drugs remain unclear, in part due to the heterogeneity of postsynaptic cells, which may respond differently to changes in serotonergic signaling. Relatively simple model systems such as Drosophila afford more tractable microcircuits in which to investigate these changes in specific cell types. Here, we focus on the mushroom body, an insect brain structure heavily innervated by serotonin and comprised of multiple different but related subtypes of Kenyon cells. We use fluorescence activated cell sorting of Kenyon cells, followed by either or bulk or single cell RNA sequencing to explore the transcriptomic response of these cells to SERT inhibition. We compared the effects of two different Drosophila Serotonin Transporter (dSERT) mutant alleles as well as feeding the SSRI citalapram to adult flies. We find that the genetic architecture associated with one of the mutants contributed to significant artefactual changes in expression. Comparison of differential expression caused by loss of SERT during development versus aged, adult flies, suggests that changes in serotonergic signaling may have relatively stronger effects during development, consistent with behavioral studies in mice. Overall, our experiments revealed limited transcriptomic changes in Kenyon cells, but suggest that different subtypes may respond differently to SERT loss-of-function. Further work exploring the effects of SERT loss-of-function in other Drosophila circuits may be used help to elucidate how SSRIs differentially affect a variety of different neuronal subtypes both during development and in adults.

show abstract

Pathway-targeting gene matrix for Drosophila gene set enrichment analysis

Cited by 6 publications

References 23 publications

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

Drosophila immune priming to Enterococcus faecalis relies on immune tolerance rather than resistance

Transcriptional changes in specific subsets of Drosophila neurons following inhibition of the serotonin transporter

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