Dataset Information

Differential transcript usage analysis of bulk and single-cell RNA-seq data with DTUrtle.

ABSTRACT:

Motivation

Each year, the number of published bulk and single-cell RNA-seq datasets is growing exponentially. Studies analyzing such data are commonly looking at gene-level differences, while the collected RNA-seq data inherently represents reads of transcript isoform sequences. Utilizing transcriptomic quantifiers, RNA-seq reads can be attributed to specific isoforms, allowing for analysis of transcript-level differences. A differential transcript usage (DTU) analysis is testing for proportional differences in a gene's transcript composition, and has been of rising interest for many research questions, such as analysis of differential splicing or cell-type identification.

Results

We present the R package DTUrtle, the first DTU analysis workflow for both bulk and single-cell RNA-seq datasets, and the first package to conduct a 'classical' DTU analysis in a single-cell context. DTUrtle extends established statistical frameworks, offers various result aggregation and visualization options and a novel detection probability score for tagged-end data. It has been successfully applied to bulk and single-cell RNA-seq data of human and mouse, confirming and extending key results. In addition, we present novel potential DTU applications like the identification of cell-type specific transcript isoforms as biomarkers.

Availability and implementation

The R package DTUrtle is available at https://github.com/TobiTekath/DTUrtle with extensive vignettes and documentation at https://tobitekath.github.io/DTUrtle/.

Supplementary information

Supplementary data are available at Bioinformatics online.

SUBMITTER: Tekath T

PROVIDER: S-EPMC8570804 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Differential transcript usage analysis of bulk and single-cell RNA-seq data with DTUrtle.

Tekath Tobias T Dugas Martin M

Bioinformatics (Oxford, England) 20211101 21

<h4>Motivation</h4>Each year, the number of published bulk and single-cell RNA-seq datasets is growing exponentially. Studies analyzing such data are commonly looking at gene-level differences, while the collected RNA-seq data inherently represents reads of transcript isoform sequences. Utilizing transcriptomic quantifiers, RNA-seq reads can be attributed to specific isoforms, allowing for analysis of transcript-level differences. A differential transcript usage (DTU) analysis is testing for pro ...[more]

PMID: 34469510

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Project description:Quantifying or labeling the sample type with high quality is a challenging task, which is a key step for understanding complex diseases. Reducing noise pollution to data and ensuring the extracted intrinsic patterns in concordance with the primary data structure are important in sample clustering and classification. Here we propose an effective data integration framework named as HCI (High-order Correlation Integration), which takes an advantage of high-order correlation matrix incorporated with pattern fusion analysis (PFA), to realize high-dimensional data feature extraction. On the one hand, the high-order Pearson's correlation coefficient can highlight the latent patterns underlying noisy input datasets and thus improve the accuracy and robustness of the algorithms currently available for sample clustering. On the other hand, the PFA can identify intrinsic sample patterns efficiently from different input matrices by optimally adjusting the signal effects. To validate the effectiveness of our new method, we firstly applied HCI on four single-cell RNA-seq datasets to distinguish the cell types, and we found that HCI is capable of identifying the prior-known cell types of single-cell samples from scRNA-seq data with higher accuracy and robustness than other methods under different conditions. Secondly, we also integrated heterogonous omics data from TCGA datasets and GEO datasets including bulk RNA-seq data, which outperformed the other methods at identifying distinct cancer subtypes. Within an additional case study, we also constructed the mRNA-miRNA regulatory network of colorectal cancer based on the feature weight estimated from HCI, where the differentially expressed mRNAs and miRNAs were significantly enriched in well-known functional sets of colorectal cancer, such as KEGG pathways and IPA disease annotations. All these results supported that HCI has extensive flexibility and applicability on sample clustering with different types and organizations of RNA-seq data.

Dataset Information

Differential transcript usage analysis of bulk and single-cell RNA-seq data with DTUrtle.

Motivation

Results

Availability and implementation

Supplementary information

Publications

Differential transcript usage analysis of bulk and single-cell RNA-seq data with DTUrtle.

Similar Datasets

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