Comprehensive expression-based isoform biomarkers predictive of drug responses based on isoform co-expression networks and clinical data

Jun, Ma; Wang, Jenny; Ghoraie, Laleh Soltan; Men, Xin; Chen, Rui; Dai, Peng

doi:10.1016/j.ygeno.2019.04.017

Cited by 15 publications

(9 citation statements)

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“…In contrast to previous isoform expression network analyses (Li et al., 2014; Ma et al., 2020), our analysis allows making a comparison of the degree to which orthologous isoforms display the same pattern of tissue bias across species. We identified 10 394 orthologous subgroups for which isoforms of the orthologous genes display a conserved tissue bias in at least two of the species analyzed.…”

Section: Discussionmentioning

confidence: 99%

Evolution of isoform‐level gene expression patterns across tissues during lotus species divergence

et al. 2022

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Both gene duplication and alternative splicing (AS) drive the functional diversity of gene products in plants, yet the relative contributions of the two key mechanisms to the evolution of gene function are largely unclear.Here, we studied AS in two closely related lotus plants, Nelumbo lutea and Nelumbo nucifera, and the outgroup Arabidopsis thaliana, for both single-copy and duplicated genes. We show that most splicing events evolved rapidly between orthologs and that the origin of lineage-specific splice variants or isoforms contributed to gene functional changes during species divergence within Nelumbo. Single-copy genes contain more isoforms, have more AS events conserved across species, and show more complex tissue-dependent expression patterns than their duplicated counterparts. This suggests that expression divergence through isoforms is a mechanism to extend the expression breadth of genes with low copy numbers. As compared to isoforms of local, small-scale duplicates, isoforms of whole-genome duplicates are less conserved and display a less conserved tissue bias, pointing towards their contribution to subfunctionalization. Through comparative analysis of isoform expression networks, we identified orthologous genes of which the expression of at least some of their isoforms displays a conserved tissue bias across species, indicating a strong selection pressure for maintaining a stable expression pattern of these isoforms. Overall, our study shows that both AS and gene duplication contributed to the diversity of gene function during the evolution of lotus.

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Section: Discussionmentioning

confidence: 99%

Evolution of isoform‐level gene expression patterns across tissues during lotus species divergence

et al. 2022

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“…However, the extent to which AS regulation creates co-expression patterns among alternative isoforms from different genes has not yet been fully addressed. Specifically, previous studies tackling this type of isoform co-expression have either focused on specific event types, such as alternative 3' exons 84 , or solely on the identification of functionally-relevant alternative isoforms in different biological contexts 85,86 .…”

Section: Discussionmentioning

confidence: 99%

Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data

Arzalluz-Luque

Salguero

Tarazona

et al. 2021

Preprint

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Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. However, the extent to which alternative isoforms establish co-expression networks that may relevant in cellular function has not been explored yet. Here, we present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships. To achieve this, we developed and validated percentile correlations, a novel approach that overcomes data sparsity and yields accurate co-expression estimates from single-cell data. Next, acorde uses correlations to cluster co-expressed isoforms into a network, unraveling cell type-specific alternative isoform usage patterns. By selecting same-gene isoforms between these clusters, we subsequently detect and characterize genes with co-differential isoform usage (coDIU) across neural cell types. Finally, we predict functional elements from long read-defined isoforms and provide insight into biological processes, motifs and domains potentially controlled by the coordination of post-transcriptional regulation.

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“…The remaining cleaned reads were aligned to the reference genome with HISAT2 (version 2.4) using “-rna-strandness RF” [ 55 ], and genes were assembled using StringTie (version 1.3.1) based on these mapped reads [ 56 ]. RSEM software was used to calculate gene expression values based on well-mapped reads and normalized to the fragments per kilobase of exon per million mapped fragment (FPKM) values, as previously described [ 57 ].…”

Section: Methodsmentioning

confidence: 99%

Comparative transcriptomic analysis of two Cucumis melo var. saccharinus germplasms differing in fruit physical and chemical characteristics

RenFan

Qin

et al. 2022

BMC Plant Biol

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Background Hami melon (Cucumis melo var. saccharinus) is a popular fruit in China because of its excellent taste, which is largely determined by its physicochemical characteristics, including flesh texture, sugar content, aroma, and nutrient composition. However, the mechanisms by which these characteristics are regulated have not yet been determined. In this study, we monitored changes in the fruits of two germplasms that differed in physicochemical characteristics throughout the fruit development period. Results Ripe fruit of the bred variety ‘Guimi’ had significantly higher soluble sugar contents than the fruit of the common variety ‘Yaolong.’ Additionally, differences in fruit shape and color between these two germplasms were observed during development. Comparative transcriptome analysis, conducted to identify regulators and pathways underlying the observed differences at corresponding stages of development, revealed a higher number of differentially expressed genes (DEGs) in Guimi than in Yaolong. Moreover, most DEGs detected during early fruit development in Guimi were associated with cell wall biogenesis. Temporal analysis of the identified DEGs revealed similar trends in the enrichment of downregulated genes in both germplasms, although there were differences in the enrichment trends of upregulated genes. Further analyses revealed trends in differential changes in multiple genes involved in cell wall biogenesis and sugar metabolism during fruit ripening. Conclusions We identified several genes associated with the ripening of Hami melons, which will provide novel insights into the molecular mechanisms underlying the development of fruit characteristics in these melons.

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Comprehensive expression-based isoform biomarkers predictive of drug responses based on isoform co-expression networks and clinical data

Cited by 15 publications

References 50 publications

Evolution of isoform‐level gene expression patterns across tissues during lotus species divergence

Evolution of isoform‐level gene expression patterns across tissues during lotus species divergence

Acorde: unraveling functionally-interpretable networks of isoform co-usage from single cell data

Comparative transcriptomic analysis of two Cucumis melo var. saccharinus germplasms differing in fruit physical and chemical characteristics

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