Trinity and Election

Tseng, Shao Kai

doi:10.5040/9780567709325

Cited by 2 publications

(2 citation statements)

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“…This is likely because of the differences in sequencing depth, discovery tool employed (i.e., bambu 11 vs. FLAIR 23 , vs Cupcake 24 ), and differences in subject age.…”

Section: Methodological and Results Overviewmentioning

confidence: 99%

Using deep long-read RNAseq in Alzheimer’s disease brain to assess medical relevance of RNA isoform diversity

Heberle,

Brandon,

Page

et al. 2023

Preprint

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Due to alternative splicing, human protein-coding genes average over eight RNA isoforms, resulting in nearly four distinct protein coding sequences per gene. Long-read RNAseq (IsoSeq) enables more accurate quantification of isoforms, shedding light on their specific roles. To assess the clinical relevance of measuring RNA isoform expression, we sequenced 12 aged human frontal cortices (6 Alzheimer's disease cases and 6 controls, 50% female) using one Oxford Nanopore PromethION flow cell per sample. Our study uncovered 53 new high-confidence RNA isoforms in clinically relevant genes, including several where the new isoform was one of the most highly expressed for that gene. Specific examples include WDR4 (61%; microcephaly), MYL3 (44%; hypertrophic cardiomyopathy), and MTHFS (25%; major depression, schizophrenia, bipolar disorder). Other notable genes with new high-confidence isoforms include CPLX2 (10%; schizophrenia, epilepsy) and MAOB (9%; targeted for Parkinson's disease treatment). We identified 1,917 clinically relevant genes expressing multiple isoforms in human frontal cortex, where 1,018 had multiple isoforms with different protein coding sequences, demonstrating the need to better understand how individual isoforms from a "single" gene are involved in human health and disease. Exactly 98 of the 1,917 genes are implicated in brain-related diseases, including Alzheimer's disease genes such as APP (A-beta; precursor protein; five), MAPT (tau protein; four), and BIN1 (eight). We also found 99 differentially expressed RNA isoforms between Alzheimer's cases and controls, despite the genes themselves not exhibiting differential expression. Our findings highlight the significant knowledge gaps in RNA isoform diversity and their clinical relevance. Deep long-read RNA sequencing will be necessary going forward to fully comprehend the clinical relevance of individual isoforms for a "single" gene. Key words: RNA isoforms, Clinical relevance, Long reads, Nanopore sequencing, Alzheimer's disease, Human brain.

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“…This is likely because of the differences in sequencing depth, discovery tool employed (i.e., bambu 11 vs. FLAIR 23 , vs Cupcake 24 ), and differences in subject age.…”

Section: Methodological and Results Overviewmentioning

confidence: 99%

Using deep long-read RNAseq in Alzheimer’s disease brain to assess medical relevance of RNA isoform diversity

Heberle,

Brandon,

Page

et al. 2023

Preprint

View full text Add to dashboard Cite

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“…We attempted to assemble the ONT direct RNA reads with existing tools, including TAMA (tc_version_date_2020_12_14) (57), Cupcake (v.29.0.0) (58), and StringTie (v1.3.4d) (59). None of the existing tools recapitulated the complexity of the bacterial transcripts accurately, leading us to develop a new algorithm for the prediction of bacterial transcripts (Figure A3).…”

Section: Assembling Ont Rna Readsmentioning

confidence: 99%

Deciphering Bacterial and Archaeal Transcriptional Dark Matter and Its Architectural Complexity

Mattick,

Bromley,

Watson

et al. 2024

Preprint

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Transcripts are potential therapeutic targets, yet bacterial transcripts remain biological dark matter with uncharacterized biodiversity. We developed and applied an algorithm to predict transcripts for Escherichia coli K12 and E2348/69 strains (Bacteria:gamma-Proteobacteria) with newly generated ONT direct RNA sequencing data while predicting transcripts for Listeria monocytogenes strains Scott A and RO15 (Bacteria:Firmicute), Pseudomonas aeruginosa strains SG17M and NN2 strains (Bacteria:gamma-Proteobacteria), and Haloferax volcanii (Archaea:Halobacteria) using publicly available data. From >5 million E. coli K12 ONT direct RNA sequencing reads, 2,484 mRNAs are predicted and contain more than half of the predicted E. coli proteins. While the number of predicted transcripts varied by strain based on the amount of sequence data used for the predictions, across all strains examined, the average size of the predicted mRNAs is 1.6-1.7 kbp while the median size of the predicted bacterial 5'- and 3'- UTRs are 30-90 bp. Given the lack of bacterial and archaeal transcript annotation, most predictions are of novel transcripts, but we also predicted many previously characterized mRNAs and ncRNAs, including post-transcriptionally generated transcripts and small RNAs associated with pathogenesis in the E. coli E2348/69 LEE pathogenicity islands. We predicted small transcripts in the 100-200 bp range as well as >10 kbp transcripts for all strains, with the longest transcript for two of the seven strains being the nuo operon transcript, and for another two strains it was a phage/prophage transcript. This quick, easy, inexpensive, and reproducible method will facilitate the presentation of operons, transcripts, and UTR predictions alongside CDS and protein predictions in bacterial genome annotation as important resources for the research community.

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Trinity and Election

Cited by 2 publications

References 0 publications

Using deep long-read RNAseq in Alzheimer’s disease brain to assess medical relevance of RNA isoform diversity

Using deep long-read RNAseq in Alzheimer’s disease brain to assess medical relevance of RNA isoform diversity

Deciphering Bacterial and Archaeal Transcriptional Dark Matter and Its Architectural Complexity

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