Upstream open reading frames may contain hundreds of novel human exons

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 23, 2024

Several recent studies have presented evidence that the human gene catalogue should be expanded to include thousands of short open reading frames (ORFs) appearing upstream or downstream existing protein-coding genes, each which would comprise an additional bicistronic transcript in humans. Here we explore alternative hypothesis explain translational and evolutionary for these ORFs without need create novel genes transcripts. We examined 2,199 been proposed as high-quality candidates determine if they could instead represent exons can added genes. checked conservation four recently sequenced, genomes, found a large majority (87.8%) conserved all expected. then looked splicing connect ORF at same locus, thus creating variant using its first exon. These protein coding exon were further evaluated structure predictions sequences included new exons. determined 582 out strong form are part gene, resulting is predicted similar better structural quality than currently annotated isoform.

Язык: Английский

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More than 2,500 coding genes in the human reference gene set still have unsettled status

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 9, 2024

Abstract In 2018 we analysed the three main repositories for human proteome, Ensembl/GENCODE, RefSeq and UniProtKB. They disagreed on coding status of one every eight annotated genes. The analysis inspired bilateral collaborations between annotation groups. Here have repeated our with updated versions reference gene sets. Superficially, little appears to changed. Although there are slightly fewer genes predicted as overall, groups still disagree 2,606 However, a comparison without read-through immunoglobulin fragments shows that sets merged or reclassified more than 700 since last just 0.6% Ensembl/GENCODE not also by other two We used features indicative non-coding examine 21,873 across found 2,000 had potential features. While some these will be protein coding, believe most likely pseudogenes. Our results suggest annotators vastly overestimate number true

Язык: Английский

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EASTR: Identifying and eliminating systematic alignment errors in multi-exon genes

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Ноя. 9, 2023

Abstract Accurate alignment of transcribed RNA to reference genomes is a critical step in the analysis gene expression, which turn has broad applications biomedical research and basic sciences. We reveal that widely used splice-aware aligners, such as STAR HISAT2, can introduce erroneous spliced alignments between repeated sequences, leading inclusion falsely transcripts RNA-seq experiments. In some cases, ‘phantom’ introns resulting from these errors make their way into widely-used genome annotation databases. To address this issue, we present EASTR (Emending Alignments Spliced Transcript Reads), software tool detects removes or files. improves accuracy across diverse species, including human, maize, Arabidopsis thaliana , by detecting sequence similarity intron-flanking regions. demonstrate applying before transcript assembly substantially reduces false positive introns, exons, transcripts, improving overall assembled transcripts. Additionally, show EASTR’s application databases detect correct likely cases mis-annotated

Язык: Английский

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Detecting differential transcript usage in complex diseases with SPIT

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Июль 10, 2023

Differential transcript usage (DTU) plays a crucial role in determining how gene expression differs among cells, tissues, and different developmental stages, thereby contributing to the complexity diversity of biological systems. In abnormal it can also lead deficiencies protein function, potentially leading pathogenesis diseases. Detecting such events for single-gene genetic traits is relatively uncomplicated; however, heterogeneity populations with complex diseases presents an intricate challenge due presence diverse causal undetermined subtypes. SPIT first statistical tool that quantifies within population identifies predominant subgroups along their distinctive sets DTU events. We provide comprehensive assessments SPIT's methodology both report results applying analyze brain samples from individuals schizophrenia. Our analysis reveals previously unreported six candidate genes.

Язык: Английский

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