ToPASeq: an R package for topology-based pathway analysis of microarray and RNA-Seq data

Ihnatová, Ivana; Budínská, Eva

doi:10.1186/s12859-015-0763-1

Cited by 40 publications

(31 citation statements)

References 24 publications

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“…Pathway analysis was performed by topology-based prediction method38 implemented in R-bioconductor package ToPAseq72. Over-representation of gene-ontology (GO terms) were analyzed using BINGO tool73.…”

Section: Methodsmentioning

confidence: 99%

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Kelleher

Burns

Behura

et al. 2016

Sci Rep

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Uterine glands are essential for pregnancy in mice and likely humans, because they secrete or transport bioactive substances that regulate uterine receptivity for blastocyst implantation. In mice, the uterus becomes receptive to blastocyst implantation on day 4, but is refractory by day 5. Here, blastocysts could be recovered from progesterone-induced uterine gland (PUGKO) but not wildtype (WT) mice on day 5 post-mating. Anti-adhesive Muc1 protein and microvilli were present on the luminal epithelium of PUGKO but not WT uteri. A number of known uterine receptivity genes and gland-specific genes were altered in the PUGKO uterus. Next, the uterus and uterine luminal fluid (ULF) were obtained from WT and PUGKO mice on day 3, 4 and 5. Transcriptome analysis revealed that 580 genes were decreased in the PUGKO uterus, however ULF secrotome analysis revealed that many proteins and several amino acids were increased in the PUGKO ULF. Of note, many proteins encoded by many gland-specific genes were not identified in the ULF of WT mice. These results support the ideas that uterine glands secrete factors that regulate ULF homeostasis and interact with other cell types in the uterus to influence uterine receptivity and blastocyst implantation for the establishment of pregnancy.

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Section: Methodsmentioning

confidence: 99%

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Kelleher

Burns

Behura

et al. 2016

Sci Rep

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“…The cluster analysis of fold enrichment of the GO terms was performed by mclust v.5 (31). The signaling pathway impact analysis (SPIA) method (34) was used to perform topology-based pathway analysis using the R and Bioconductor package ToPASeq (35). The DE genes were used as a query to predict receptor and corresponding ligands from the FANTOM5 database of receptors and ligands (Riken, Tokyo, Japan) (36).…”

Section: Functional Annotation Of Differentially Regulated Genesmentioning

confidence: 99%

Evidence for functional interactions between the placenta and brain in pregnant mice

2018

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The placenta plays a pivotal role in the development of the fetal brain and also influences maternal brain function, but our understanding of communication between the placenta and brain remains limited. Using a gene expression and network analysis approach, we provide evidence that the placenta transcriptome is tightly interconnected with the maternal brain and fetal brain in d 15 pregnant C57BL/6J mice. Activation of serotonergic synapse signaling and inhibition of neurotrophin signaling were identified as potential mediators of crosstalk between the placenta and maternal brain and fetal brain, respectively. Genes encoding specific receptors and ligands were predicted to affect functional interactions between the placenta and brain. Paralogous genes, such as sex comb on midleg homolog 1/scm‐like with 4 mbt domains 2 and polycomb group ring finger (Pcgf) 2/Pcgf5, displayed antagonistic regulation between the placenta and brain. Additionally, conditional ablation of forkhead box a2 (Foxa2) in the glands of the uterus altered the transcriptome of the d 15 placenta, which provides novel evidence of crosstalk between the uterine glands and placenta. Furthermore, expression of cathepsin 6 and monocyte to macrophage differentiation associated 2 was significantly different in the fetal brain of Foxa2 conditional knockout mice compared with control mice. These findings provide a better understanding of the intricacies of uterus‐placenta‐brain interactions during pregnancy and provide a foundation and model system for their exploration.—Behura, S. K., Kelleher, A. M., Spencer, T. E. Evidence for functional interactions between the placenta and brain in pregnant mice. FASEB J. 33, 4261–4272 (2019). http://www.fasebj.org

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“…The PEA was conducted using the R-package "To-PASeq" (Ihnatova and Budinska, 2015), adapted for RNA-seq data. Because PEA is a network-based approach, it is only applicable for signaling pathways with gene network information (inhibition/activation).…”

Section: Differential Gene Expression and Gene Set Enrichment Analysesmentioning

confidence: 99%

Liver transcriptome analysis reveals important factors involved in the metabolic adaptation of the transition cow

Drögemüller

Reimer

et al. 2017

Journal of Dairy Science

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During early lactation, dairy cows experience a severe metabolic load often resulting in the development of various diseases. The inevitable deficiency in nutrients and energy at the onset of lactation requires an optimal adaptation of the hepatic metabolism to overcome metabolic stress. We conducted a whole-liver transcriptome analysis for the transition cow to identify novel factors crucial for metabolic adaptation. Liver samples were obtained from 6 Red Holstein dairy cows (parity 2 to 7, mean ± standard deviation: 3.7 ± 2.3) at 3 time points: T1 = 22 ± 4 d antepartum, T2 = 10 ± 2 d postpartum, and T3 = 17 ± 2 d postpartum. Using RNA sequencing (RNA-seq), we studied the transcriptomic profile of the transition cow before and after parturition. We performed a differential gene expression analysis (DGEA) and gene-set enrichment analysis (GSEA) for biological processes (gene ontology, GO) and pathways (Kyoto Encyclopedia of Genes and Genomes, KEGG). Among the 10,186 expressed genes, we discovered 1,063 differentially expressed genes (false discovery rate = 5%). The GSEA revealed 16 biological processes and 7 pathways significantly (false discovery rate = 5%) associated with the hepatic changes of the transition cow. Our results confirm that major hepatic changes are related to energy mobilization after parturition; in particular, they are related to fatty acid oxidation/metabolism, cholesterol metabolism, and gluconeogenesis. Using the STRING database (https://string-db.org/), we investigated interactions between significant genes and identified 9 key genes (CYP7A1, APOA1, CREM, LOC522146, CYP2C87, HMGCR, FDFT1, SGLE, and CYP26A1) through which the different processes involved in the metabolic adaptation interact. Comparing our main results with the literature, we could identify further genes that have not yet been associated with the transition period (e.g., CPT1B, ADIPOR2, LEPR, CREB3L3, and CCND1) and that are mainly involved in processes controlled by AMP-activated protein kinase, an important regulator of energy homeostasis.

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ToPASeq: an R package for topology-based pathway analysis of microarray and RNA-Seq data

Cited by 40 publications

References 24 publications

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation

Evidence for functional interactions between the placenta and brain in pregnant mice

Liver transcriptome analysis reveals important factors involved in the metabolic adaptation of the transition cow

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