<i>TimiRGeN</i>: <i>R/Bioconductor</i> package for time series microRNA–mRNA integration and analysis

Patel, Krutik; Chandrasegaran, Sharmilla; Clark, Ian M.; Proctor, Carole J.; Young, David A.; Shanley, Daryl P.

doi:10.1093/bioinformatics/btab377

Cited by 8 publications

(6 citation statements)

References 68 publications

(75 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the published studies, let-7c-5p and miR-181b-5p were shown to be closely associated with the invasion and migration of cancer (26)(27)(28). To verify whether lack of let-7c-5p and miR-181b-5p was critical for promoting the migration and invasion of BEAS-2B cells, miRNA inhibitors were employed to lessen the expression of let-7c-5p and miR-181b-5p in BEAS-2B cells.…”

Section: Combined Effect Of Let-7c-5p and Mir-181b-5p On Migration An...mentioning

confidence: 99%

Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p

Liu

Yan

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

As carriers containing abundant biological information, exosomes could deliver the property of donor cells to recipient cells. Emerging studies have shown that tumor cells could secrete a mass of exosomes into the microenvironment to regulate bystander cells. However, the underlying mechanisms of such a phenomenon remain largely unexplored. In this research, we purified and identified the exosomes of A549 cells and found that A549-cell-derived exosomes promoted BEAS-2B cells migration, invasion, and epithelial–mesenchymal transition (EMT). Importantly, we observed that let-7c-5p and miR-181b-5p were attenuated in A549-cell-derived exosomes compared to BEAS-2B-cell-derived exosomes. The analysis of miRNA expression level in BEAS-2B cells indicated that incubation with A549-cell-derived exosomes reduced the expression levels of let-7c-5p and miR-181b-5p. In transient transfections assay, we found that downregulation of let-7c-5p and miR-181b-5p simultaneously showed stronger promotion of BEAS-2B cells migration and invasion than individually. Moreover, exosomes secreted from A549 cells with upregulated expression of let-7c-5p and miR-181b-5p significantly reduce their regulatory effect on BEAS-2B cells. Bioinformatics analyses revealed that let-7c-5p and miR-181b-5p inhibit the EMT process mainly by regulating focal adhesion and mitogen-activated protein kinase (MAPK) signaling pathway. Thus, our data demonstrated that A549-cell-derived exosomal let-7c-5p and miR-181b-5p could induce migration, invasion, and EMT in BEAS-2B cells, which might be regulated through focal adhesion and MAPK signaling pathway. The expression level of let-7c-5p and miR-181b-5p may show great significance for the early diagnosis of lung cancer.

show abstract

Section: Combined Effect Of Let-7c-5p and Mir-181b-5p On Migration An...mentioning

confidence: 99%

Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p

Liu

Yan

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

show abstract

“…Analysis with TimiRGeN identified miR-199b-5p to be upregulated during chondrogenesis Our previously generated 14-day chondrogenesis time series dataset was analysed with the TimiRGeN R/ Bioconductor package -a novel tool we developed to analyse longitudinal miRNA-mRNA expression datasets 10,17 . Prior to using TimiRGeN, the transcriptomic data underwent timepoint based differential expression analysis, using the day 0 time-point (MSCs) as the control group for chondrogenesis samples measured at days: 1, 3, 6, 10, 14, and thus created differential expression data over five timepoints.…”

Section: Resultsmentioning

confidence: 99%

“…All data wrangling and processing took place in R.Analysis with the TimiRGeN R package. Dataframes containing mRNA and miRNA DE results are analysed using the combined mode of TimiRGeN17 . The threshold for timepoint specific gene filtration was set as <0.05 and adjusted P values were used for filtration.…”

mentioning

confidence: 99%

Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis

Patel

Barter

Soul

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Changes chondrocyte gene expression can contribute to the development of osteoarthritis (OA), and so better understanding of the regulative processes during chondrogenesis can highlight potential drug targets for OA. microRNAs (miRNAs) have been a focus of chondrogenesis/ OA research and we have used a combined experimental, bioinformatic, and systems biology approach to explore multiple miRNA-mRNA interactions that regulate chondrogenesis. We identified paralogues miR-199a-5p and miR-199b-5p as pro-chondrogenic regulators of chondrogenesis through bioinformatic analysis. Experimental work demonstrated alteration of miR-199a-5p or miR-199b-5p expression led to significant inverse modulations of chondrogenic biomarkers: ACAN, COL2A1, SOX9 and glycosaminoglycan levels. Potential miR-199a/b-5p targets were then identified using RNAseq combined with bioinformatic analysis to identify FZD6, ITGA3 and CAV1 as highly likely candidates. Through knockdown experiments we indicated a strong antagonistic relationship between miR-199a/b-5p and FZD6, ITGA3 and CAV1. Luciferase assays using FZD6 and ITGA3 3'UTRs luciferase assays indicated both mRNAs to be targets of miR-199a-5p. The experimental work was used to generate and parameterize a multi-miRNA 14-day chondrogenesis kinetic model to be used as a repository for the experimental work and as a resource for further investigation of this system. This is the first multi-miRNA model of any system, and it highlights that many other miRNAs may be involved in the regulation of this system and was used to predict experimental gaps not covered by experimental work.

show abstract

“…Genes with a Benjimini-Hochberg FDR of <0.05 were kept. Significantly expressed genes from the gender based DE analysis was taken forward for miRNA-mRNA integrated analysis with the TimiRGeN R package for pathway enrichment analysis (Patel et al 2021).…”

Section: Initial Data Explorationmentioning

confidence: 99%

“…The initial data generation and analysis paper showed striatal neuron samples had greater gene expression changes than cortical neuron samples, however we were more interested in cortical samples as cortical loss has been seen as an early pathological event of HD and this would be useful for our predisposition detection queries (Rosas et al 2002). Initial data exploration with differential expression (DE) analysis and the TimiRGeN R package identified a batch effect in the data, high homology, and some gender differences (Patel et al 2021). Based on this, the data was corrected (batch effect removed, gender differences reduced) and re-labelled so that JOHD and WT samples could be differentiated using ML.…”

Section: Introductionmentioning

confidence: 99%

Using Machine Learning to identify microRNA biomarkers for predisposition to Huntington’s Disease

Patel

Sheridan

Shanley

2022

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Juvenile-Onset Huntington's disease (JOHD) is a rare form of Huntington's disease (HD) which leads to chronic neurodegeneration which begins prior to the age of 25. Like HD, JOHD is triggered by a large expansion of CAG nucleotides in the HTT gene which leads to neurotoxicity and aberrant gene expression. However, unlike HD, in JOHD the relationship between the length of CAG expansion and age of disease onset is non-linear. Thus, it would be of interest to identify molecular biomarkers which indicate predisposition to the development of JOHD, and as microRNAs (miRNAs) circulate in bio-fluids they would be particularly useful biomarkers. Methods: We explored a large JOHD miRNA-mRNA expression dataset (GSE65776) to establish appropriate questions that could be addressed using Machine Learning (ML). We sought sets of features (mRNAs/miRNAs) to predict JOHD or WT samples from aged or young mouse cortex samples, and we asked if a set of features could predict predisposition to JOHD or WT genotypes by training models on aged samples and testing the models on young samples. We used a k-best strategy which included oversampling for unbalanced classes, min_max scaling and 5-fold cross-validation. Several models were created using ADAboost, ExtraTrees, GaussianNB and Random Forest, and the best performing models were further analysed using AUC curves and PCA plots. Finally, genes used to train our miRNA-based predisposition model were compared to HD patient bio-fluid samples. Results: Our testing accuracies were between 66-100% and AUC scores were between 31-100%. We generated several excellent models with testing accuracies >80% and AUC scores>90%. We also identified homologues of mmu-miR-154-5p, mmu-miR-181a-5p and mmu-miR-212-3p, mmu-miR-378b, mmu-miR-382-5p and mmu-miR-770-5p to be circulating in HD patient blood samples at p.values of <0.05. Conclusions: We generated several age-based models which could differentiate between JOHD and WT samples, including an aged mRNA-based model with a 100% AUC score. We also identified several miRNAs used to train our miRNA-based predisposition model which were detectable in HD patient blood samples, which suggests they could be potential candidates for use as non-invasive biomarkers for JOHD/ HD research.

show abstract

TimiRGeN: R/Bioconductor package for time series microRNA–mRNA integration and analysis

Cited by 8 publications

References 68 publications

Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p

Exosomes of A549 Cells Induced Migration, Invasion, and EMT of BEAS-2B Cells Related to let-7c-5p and miR-181b-5p

Systems analysis of miR-199a/b-5p and multiple miR-199a/b-5p targets during chondrogenesis

Using Machine Learning to identify microRNA biomarkers for predisposition to Huntington’s Disease

Contact Info

Product

Resources

About