Quantifying transcriptome diversity: a review

Jones, Emma F; Haldar, Anisha; Oza, Vishal; Lasseigne, Brittany N.

doi:10.1093/bfgp/elad019

Cited by 8 publications

(4 citation statements)

References 163 publications

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“…Inter-subject variability is an important challenge when analyzing immune response to vaccines. Variability in gene expression of human populations have been observed in many studies (reviewed in 34 ) and the causes are not well understood. However, gene polymorphisms, differences in gene methylation due to age, sex, and environmental factors are all considered contributing factors.…”

Section: Discussionmentioning

confidence: 99%

Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites

Mura,

Misganaw,

Gautam

et al. 2023

Human Vaccines & Immunotherapeutics

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The identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools are key to not only identify correlates of protection but also biomarkers of disease susceptibility. The current study expands our previous cellular and serological profiling of vaccine-induced responses to a whole parasite malaria vaccine. The irradiated sporozoite model was chosen as it is considered the most effective vaccine against malaria. In contrast to whole blood transcriptomics analysis, we stimulated peripheral blood mononuclear cells (PBMC) with sporozoites and enriched for antigen-specific cells prior to conducting transcriptomics analysis. By focusing on transcriptional events triggered by antigen-specific stimulation, we were able to uncover quantitative and qualitative differences between protected and non-protected individuals to controlled human malaria infections and identified differentially expressed genes associated with sporozoite-specific responses. Further analyses including pathway and gene set enrichment analysis revealed that vaccination with irradiated sporozoites induced a transcriptomic profile associated with Th1-responses, Interferon-signaling, antigen-presentation, and inflammation. Analyzing longitudinal time points not only post-vaccination but also post-controlled human malaria infection further revealed that the transcriptomic profile of protected vs non-protected individuals was not static but continued to diverge over time. The results lay the foundation for comparing protective immune signatures induced by various vaccine platforms to uncover immune correlates of protection that are common across platforms.

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Section: Discussionmentioning

confidence: 99%

Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites

Mura,

Misganaw,

Gautam

et al. 2023

Human Vaccines & Immunotherapeutics

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“…The range of diversity and specificity is between 0 and 1, with 0 being low and 1 being high. Another important thing to note is that they are inversely related ( Jones et al 2023 ). Thus, a highly diverse gene will have similar expression across tissues but low specificity.…”

Section: Methodsmentioning

confidence: 99%

CoSIA: an R Bioconductor package for CrOss Species Investigation and Analysis

Haldar,

Oza,

DeVoss

et al. 2023

Bioinformatics

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Summary High-throughput sequencing technologies have enabled cross-species comparative transcriptomic studies; however, there are numerous challenges for these studies due to biological and technical factors. We developed CoSIA (Cross-Species Investigation and Analysis), a Bioconductor R package and Shiny app that provides an alternative framework for cross-species transcriptomic comparison of non-diseased wild-type RNA sequencing gene expression data from Bgee across tissues and species (human, mouse, rat, zebrafish, fly, and nematode) through visualization of variability, diversity, and specificity metrics. Availability and implementation https://github.com/lasseignelab/CoSIA.

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“…While short-read gene expression AS data analysis can include calculating the percent spliced-in of exons or the splice junctions for a given gene, long reads enable researchers to quantify splicing across entire transcripts directly. Differential transcript usage (DTU), sometimes referred to as differential isoform usage, quantifies changes in transcript expression as a fraction of the overall expression of a particular gene, complementing differential gene expression (DGE) and differential transcript expression (DTE) analyses (14). Recently, researchers identified six candidate genes with novel DTU events in a schizophrenia cohort and developed a method to stratify patient populations using multi-gene DTU patterns (15), exemplifying that DTU can identify biologically relevant information in heterogeneous patient populations.…”

Section: Introductionmentioning

confidence: 99%

Long-read RNA sequencing identifies region- and sex-specific C57BL/6J mouse brain mRNA isoform expression and usage

Jones,

Howton,

Flanary

et al. 2024

Preprint

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Alternative splicing (AS) contributes to the biological heterogeneity between species, sexes, tissues, and cell types. Many diseases are either caused by alterations in AS or by alterations to AS. Therefore, measuring AS accurately and efficiently is critical for assessing molecular phenotypes, including those associated with disease. Long-read sequencing enables more accurate quantification of differentially spliced isoform expression than short-read sequencing approaches, and third-generation platforms facilitate high-throughput experiments. To assess differences in AS across the cerebellum, cortex, hippocampus, and striatum by sex, we generated and analyzed Oxford Nanopore Technologies (ONT) long-read RNA sequencing (lrRNA-Seq) C57BL/6J mouse brain cDNA libraries. From >85 million reads that passed quality control metrics, we calculated differential gene expression (DGE), differential transcript expression (DTE), and differential transcript usage (DTU) across brain regions and by sex. We found significant DGE, DTE, and DTU across brain regions and that the cerebellum had the most differences compared to the other three regions. Additionally, we found region-specific differential splicing between sexes, with the most sex differences in DTU in the cortex and no DTU in the hippocampus. We also report on two distinct patterns of sex DTU we observed, sex-divergent and sex-specific, that could potentially help explain sex differences in the prevalence and prognosis of various neurological and psychiatric disorders in future studies. Finally, we built a Shiny web application for researchers to explore the data further. Our study provides a resource for the community; it underscores the importance of AS in biological heterogeneity and the utility of long-read sequencing to better understand AS in the brain.

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Quantifying transcriptome diversity: a review

Cited by 8 publications

References 163 publications

Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites

Human transcriptional signature of protection after Plasmodium falciparum immunization and infectious challenge via mosquito bites

CoSIA: an R Bioconductor package for CrOss Species Investigation and Analysis

Long-read RNA sequencing identifies region- and sex-specific C57BL/6J mouse brain mRNA isoform expression and usage

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