Seiðr: Efficient calculation of robust ensemble gene networks

Schiffthaler, Bastian; Zalen, Elena van; Serrano, Alonso; Street, Nathaniel R.; Delhomme, Nicolas

doi:10.1016/j.heliyon.2023.e16811

Cited by 11 publications

(5 citation statements)

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“…In this study, we used a comprehensive array of gene co-expression network inference algorithms, facilitated by the Seidr toolkit [ 37 ], to delineate the core genes associated with IVM response in P . univalens .…”

Section: Methodsmentioning

confidence: 99%

“…For this analysis, we only considered genes that exhibited non-zero total read counts. To identify highly correlated genes that potentially share similar biological functions, pathways, or are co-regulated, we performed gene co-expression network analysis using the Seidr tool kit [ 37 ]. Before running the gene co-expression analysis, count data was processed by applying variance stabilizing transformation from the DESeq2 R package (v1.34.0) [ 49 ] to normalize across samples and by using the limma R package (v3.50.3) [ 50 ] to mitigate batch effects based on the above model design.…”

Section: Methodsmentioning

confidence: 99%

“…Conventional candidate gene approaches [ 13 , 22 , 30 – 33 ], often biased by selectively choosing candidates from existing literature or based solely on the expression levels, are constrained by their reliance on pre-existing knowledge, limiting the discovery of novel candidates. In contrast, the rise of data-driven analytical methods, including both supervised and unsupervised techniques [ 34 – 36 ], such as those used in gene network building and analysis [ 37 , 38 ], facilitate a more objective exploration of gene functions and interactions. These methods provide insights into the multifaceted gene relationships that govern drug response and/or resistance, without the predispositions inherent in conventional approaches.…”

Section: Introductionmentioning

confidence: 99%

“…These methods provide insights into the multifaceted gene relationships that govern drug response and/or resistance, without the predispositions inherent in conventional approaches. For instance, the Seidr toolkit [ 37 ], a paradigm of such unbiased methodologies, was recently utilized to construct a gene network for Norway spruce ( Picea abies ) under drought conditions, successfully pinpointing key genes and inferring functions for uncharacterized ones [ 37 ]. This example illustrates Seidr’s capacity for conducting comprehensive gene network analyses, which can be instrumental in deciphering complex biological phenomena, including drug responses and resistance mechanisms in parasitic nematodes.…”

Section: Introductionmentioning

confidence: 99%

“…univalens adult worms exposed in vitro to IVM at concentrations of 10 −9 M and 10 −11 M for 24 hours. Leveraging the Seidr toolkit [ 37 ], we adopted a less biased, data-driven gene network approach to systematically identify and evaluate the core genes underlying IVM response and potential resistance mechanisms in the nerve-dominated anterior region and the metabolically active intestinal tissue.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure

Dube,

Delhomme,

Martin

et al. 2024

PLoS ONE

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure

Dube,

Delhomme,

Martin

et al. 2024

PLoS ONE

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The circadian clock participates in seasonal growth in Norway spruce (Picea abies)

Lázaro-Gimeno,

Ferrari,

Delhomme

et al. 2024

Tree Physiology

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The boreal forest ecosystems of the northern hemisphere are dominated by conifers, of which Norway spruce (Picea abies (L.) H. Karst.) is one of the most common species. Due to its economic interest to the agroforestry industry, as well as its ecological significance, it is important to understand seasonal growth and biomass production in Norway spruce. Solid evidence that the circadian clock regulates growth in conifers has proved elusive, however, resulting in significant gaps in our knowledge of clock function in these trees. Here, we reassess the impact of the circadian clock on growth in Norway spruce. Using a combination of approaches monitoring the physiology of vegetative growth, transcriptomics and bioinformatics, we determined that the clock could be participating a decisive role in enabling growth, acting in specific developmental processes influenced by season and geographical location to guide bud burst and growth. Thus, evidences indicate that there is time for spruce.

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Gene co-expression network analysis reveal core responsive genes inParascaris univalenstissues following ivermectin exposure

Dube,

Delhomme,

Martin

et al. 2023

Preprint

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Anthelmintic resistance in equine parasiteParascaris univalens, compromises ivermectin (IVM) effectiveness and necessitates an in-depth understanding of its resistance mechanisms. Most research, primarily focused on holistic gene expression analyses, may overlook vital tissue-specific responses and often limit the scope of novel genes. This study leveraged gene co-expression network analysis to elucidate tissue-specific transcriptional responses and to identify core genes implicated in the IVM response inP. univalens. Adult worms (n=28) were exposed to 10-11M and 10-9M IVMin vitrofor 24 hours. RNA-sequencing examined transcriptional changes in the anterior end and intestine. Differential expression analysis revealed pronounced tissue differences, with the intestine exhibiting substantially more IVM-induced transcriptional activity. Gene co-expression network analysis identified seven modules significantly associated with the response to IVM. Within these, 219 core genes were detected, largely expressed in the intestinal tissue and spanning diverse biological processes with unspecific patterns. After 10-11M IVM, intestinal tissue core genes showed transcriptional suppression, cell cycle inhibition, and ribosomal alterations. Interestingly, genesPgR028_g047(sorb-1),PgB01_g200(gmap-1) andPgR046_g017(col-37&col-102) switched from downregulation at 10-11M to upregulation at 10-9M IVM. The 10-9M concentration induced expression of cuticle and membrane integrity core genes in the intestinal tissue. No clear core gene patterns were visible in the anterior end after 10-11M IVM. However, after 10-9M IVM, the anterior end mostly displayed downregulation, indicating disrupted transcriptional regulation. One interesting finding was the non-modular calcium-signaling gene,PgR047_g066 (gegf-1), which uniquely connected 71 genes across four modules. These genes were enriched for transmembrane signaling activity, suggesting thatPgR047_g066 (gegf-1)could have a key signaling role. By unveiling tissue-specific expression patterns and highlighting biological processes through unbiased core gene detection, this study reveals intricate IVM responses inP. univalens. These findings suggest alternative drug uptake of IVM and can guide functional validations to further IVM resistance mechanism understanding.Author summaryIn our study, we tackled the challenge of understanding how the equine roundwormParascaris univalenshas become resistant to ivermectin (IVM). We exposed adult worms in laboratory conditions to IVM and thereafter dissected two tissues, the frontal part and the intestine of the worm. We used gene networks and focused on how these two tissues respond at the genetic level to exposure of IVM. We discovered that the response to IVM is highly tissue-specific. The intestinal tissue, in particular, showed a much stronger reaction to the drug compared to the frontal part of the worm. We identified 219 key genes, mainly in the intestinal tissue, involved in various biological functions that play a crucial role in how the parasite deals with IVM. Interestingly, we found a decrease in gene activity leading to cellular disruptions at lower drug concentration, whereas genes responsible for maintaining the worm’s structural integrity were triggered at high concentration. One of our significant finding was the identification of,PgR047_g066 (gegf-1), which seems to act as a master regulator, coordinating the response of numerous other genes. This finding opens new avenues for understanding the complex ways in whichP. univalensrespond to drug treatment. Our research not only sheds light on the specific waysP. univalensresponds to IVM, but it also demonstrates the power of looking at gene networks to uncover new and important genes. These insights can be crucial for developing new strategies to combat drug resistance in parasites, a matter of great importance in both veterinary and human medicine.

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Seiðr: Efficient calculation of robust ensemble gene networks

Cited by 11 publications

References 53 publications

Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure

Gene co-expression network analysis reveal core responsive genes in Parascaris univalens tissues following ivermectin exposure

The circadian clock participates in seasonal growth in Norway spruce (Picea abies)

Gene co-expression network analysis reveal core responsive genes inParascaris univalenstissues following ivermectin exposure

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