Genenames.org: the HGNC resources in 2023

Seal, Ruth L.; Braschi, Bryony; Gray, Kristian; Jones, Tamsin E. M.; Tweedie, Susan; Haim-Vilmovsky, Liora; Bruford, Elspeth A.

doi:10.1093/nar/gkac888

Cited by 182 publications

(155 citation statements)

References 36 publications

(34 reference statements)

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“…due to off-target effects). Importantly, there are over 56 known genes within the complement system (see Supplementary Information ) 65 , highlighting the need for a systematic, evidence-based approach to identify effective gene targets.…”

Section: Discussionmentioning

confidence: 99%

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Murphy

Gordon-Smith

Chapman

et al. 2023

Preprint

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Rare diseases (RDs) are uncommon as individual diagnoses, but as a group contribute to an enormous disease burden globally. However, partly due the low prevalence and high diversity of individual RDs, this category of diseases is understudied and under-resourced. The advent of large, standardised genetics databases has enabled high-throughput, comprehensive approaches that uncover new insights into the multi-scale aetiology of thousands of diseases. Here, using the Human Phenotype Ontology (9,677 annotated phenotypes) and multiple single-cell transcriptomic atlases (77 human cell types and 38 mouse cell types), we conducted >688,000 enrichment tests (x100,000 bootstrap iterations each) to identify >13,888 genetically supported cell type-phenotype associations. Our results recapitulate well-known cell type-phenotype relationships, and extend our understanding of these diseases by pinpointing the genes linking phenotypes to specific cell (sub)types. We also reveal novel cell type-phenotype relationships across disparate branches of clinical disease (e.g. the nervous, cardiovascular, and immune systems). Next, we introduce a computational pipeline to prioritise gene targets with high cell type-specificity to minimise off-target effects and maximise therapeutic potential. To broaden the impact of our study, we have released two R packages to fully replicate our analyses, as well as a series of interactive web apps so that stakeholders from a variety of backgrounds may further explore and utilise our findings. Together, we present a promising avenue for systematically and robustly uncovering the multi-scale aetiology of RDs at scale.

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Section: Discussionmentioning

confidence: 99%

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Murphy

Gordon-Smith

Chapman

et al. 2023

Preprint

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“…The gene annotation for analyses of human genetic data was the gencode annotation v22, while the gene annotation for analyses of mouse data was the gencode annotation vM23 52 . Both gencode annotations were filtered first to only include transcripts marked as "protein coding" and subsequently to only include the 17153 genes for which a one-to-one ortholog could be identified between mouse and human using the HCOP fifteen-column orthology table (downloaded on the 06.01.2020 from the HGNC database 53 ). The gene annotation for the analysis of TCGA expression data was the gencode annotation v22 and the gene annotation for the analysis of GTEx expression data was the gencode annotation v26.…”

Section: Reference Genomes and Gene Definitionsmentioning

confidence: 99%

Functional synapses between small cell lung cancer and glutamatergic neurons

Schmitt

Sakthivelu

Ndoci

et al. 2023

Preprint

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Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer, characterized by rapid proliferation, early metastatic spread, clinical recurrence and high rate of mortality. Using in vivo insertional mutagenesis screening in conjunction with cross-species genomic and transcriptomic validation, we identified a strong and consistent signal for neuronal, synaptic, and glutamatergic signaling gene sets in murine and human SCLC. We show that SCLC cells have the ability to develop intimate contacts with neuronal glutamatergic terminals in vitro, in autochthonous primary lung tumors and in brain-engrafted tumors. These contacts can develop into bona fide synapses, allowing SCLC cells to receive glutamatergic inputs. Fitting with a potential oncogenic role of neuron-SCLC interactions, we show that SCLC cells derive a robust proliferation advantage when co-cultured with neurons. Moreover, the repression of glutamate release and the stimulation of the inhibitory glutamate receptor GRM8 displayed therapeutic efficacy in an autochthonous mouse model of SCLC. Therefore, following malignant transformation, SCLC cells appear to hijack glutamatergic signaling to sustain tumor growth, thereby exposing a novel entry route for therapeutic intervention.

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“…The LC peak areas were exported into Excel and the abundance of the top 3 ionizing peptides from each protein isoform of interest were used to quantify protein abundances. Results were manually curated to remove redundant peaks and gene names were curated to follow the HGNC nomenclature 52 . After removing redundant entries, LC peaks were normalized to the total sum of peaks and Histone H4 (Uniprot accession: B5FXC8) (Supplemental table S2).…”

Section: Proteomicsmentioning

confidence: 99%

Peak performance singing requires daily vocal exercise in songbirds

Adam

Riebel

Stål

et al. 2023

Preprint

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Vocal signals mediate much of human and non-human communication. Key performance traits - such as repertoire size, speed and accuracy of delivery - affect communication efficacy in fitness-decisive contexts such as mate choice and resource competition1. Specialized fast vocal muscles2,3 are central to accurate sound production4, but it is unknown whether vocal, like limb muscles5,6, need exercise to gain and maintain peak performance7,8. Here, we show that for song development in juvenile songbirds, the closest analogue to human speech acquisition9, regular vocal muscle exercise is crucial to achieve adult peak muscle performance. Furthermore, adult vocal muscle performance reduces within two days of abolishing exercise, leading to downregulation of critical proteins transforming fast to slower muscle fibre types. Daily vocal exercise is thus required to both gain and maintain peak vocal muscle performance, and if absent changes vocal output. We show that conspecifics can detect these acoustic changes and females prefer the song of exercised males. Song thus contains information on recent exercise status of the sender. Daily investment in vocal exercise to maintain peak performance is an unrecognized cost of singing and could explain why many birds sing daily even under adverse conditions10. Because neural regulation of syringeal and laryngeal muscle plasticity is equivalent, vocal output may reflect recent exercise status in all vocalizing vertebrates.

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Genenames.org: the HGNC resources in 2023

Cited by 182 publications

References 36 publications

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Identification of cell type-specific gene targets underlying thousands of rare diseases and subtraits

Functional synapses between small cell lung cancer and glutamatergic neurons

Peak performance singing requires daily vocal exercise in songbirds

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