HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed abstracts

Dholakia, Dhwani; Kalra, Ankit; Misir, Bishnu Raman; Kanga, Uma; Mukerji, Mitali

doi:10.1186/s12864-021-08239-0

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…Drawn from UCSC browser annotation, vertical bars represent exons and arrowheads direction of transcription. ( C ) Sunburst plot of documented disease associations with SNP variation in the vicinity of HLA-DQA1, highlighting JIA, plotted with HLA-spread ( http://hla-spread.igib.res.in ) [ 42 ]. Rings indicate increasing levels of haplotype resolution and each ray is a disease sub-type within the broader category …”

Section: Resultsmentioning

confidence: 99%

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing

et al. 2023

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Background Juvenile Idiopathic Arthritis (JIA) is an autoimmune disease with a heterogenous clinical presentation and unpredictable response to available therapies. This personalized transcriptomics study sought proof-of-concept for single-cell RNA sequencing to characterize patient-specific immune profiles. Methods Whole blood samples from six untreated children, newly diagnosed with JIA, and two healthy controls were cultured for 24 h with or without ex vivo TNF stimulation and subjected to scRNAseq to examine cellular populations and transcript expression in PBMCs. A novel analytical pipeline, scPool, was developed wherein cells are first pooled into pseudocells prior to expression analysis, facilitating variance partitioning of the effects of TNF stimulus, JIA disease status, and individual donor. Results Seventeen robust immune cell-types were identified, the abundance of which was significantly affected by TNF stimulus, which resulted in notable elevation of memory CD8 + T-cells and NK56 cells, but down-regulation of naïve B-cell proportions. Memory CD8 + and CD4 + T-cells were also both reduced in the JIA cases relative to two controls. Significant differential expression responses to TNF stimulus were also characterized, with monocytes showing more transcriptional shifts than T-lymphocyte subsets, while the B-cell response was more limited. We also show that donor variability exceeds the small degree of possible intrinsic differentiation between JIA and control profiles. An incidental finding of interest was association of HLA-DQA2 and HLA-DRB5 expression with JIA status. Conclusions These results support the development of personalized immune-profiling combined with ex-vivo immune stimulation for evaluation of patient-specific modes of immune cell activity in autoimmune rheumatic disease.

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Section: Resultsmentioning

confidence: 99%

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing

et al. 2023

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“…Crohn’s disease was the phenotype with the least associations (1), but the other phenotypes averaged 35.9 associations at the 3-field resolution, with the highest number of associations in auto-immune thyroid disorders ( n = 69), coeliac disease ( n = 63), and psoriasis ( n = 62). To test how many of these associations were novel, we used the HLA-SPREAD PubMed abstract natural language processing database 39 . An association was considered previously reported if we could find it in the database.…”

Section: Resultsmentioning

confidence: 99%

“…We used two sources to determine if an allele association was novel. We first used the HLA-SPREAD database 39 , which used a natural language processing algorithm to scan 28 million PubMed abstracts for HLA allele associations. If an allele association was reported in the database, it was not deemed novel.…”

Section: Methodsmentioning

confidence: 99%

HLA allele-calling using multi-ancestry whole-exome sequencing from the UK Biobank identifies 129 novel associations in 11 autoimmune diseases

Butler-Laporte,

Farjoun,

Nakanishi

et al. 2023

Commun Biol

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The human leukocyte antigen (HLA) region on chromosome 6 is strongly associated with many immune-mediated and infection-related diseases. Due to its highly polymorphic nature and complex linkage disequilibrium patterns, traditional genetic association studies of single nucleotide polymorphisms do not perform well in this region. Instead, the field has adopted the assessment of the association of HLA alleles (i.e., entire HLA gene haplotypes) with disease. Often based on genotyping arrays, these association studies impute HLA alleles, decreasing accuracy and thus statistical power for rare alleles and in non-European ancestries. Here, we use whole-exome sequencing (WES) from 454,824 UK Biobank (UKB) participants to directly call HLA alleles using the HLA-HD algorithm. We show this method is more accurate than imputing HLA alleles and harness the improved statistical power to identify 360 associations for 11 auto-immune phenotypes (at least 129 likely novel), leading to better insights into the specific coding polymorphisms that underlie these diseases. We show that HLA alleles with synonymous variants, often overlooked in HLA studies, can significantly influence these phenotypes. Lastly, we show that HLA sequencing may improve polygenic risk scores accuracy across ancestries. These findings allow better characterization of the role of the HLA region in human disease.

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“…These variants may centrally influence thymic selection or affect the binding affinity of epitopes peripherally, ultimately increasing the repertoire of recognized allo- and autoepitopes and expanding the pool of reactive T and B cells. Consequently, polymorphisms within HLA loci may enhance immune defenses against pathogens but also increase the risk of developing autoimmune diseases [ 21 ]. HLA genes may actually affect the survival of T cells with specific patterns in the complementarity determining region 3 (CDR3) of the TCR, characterized by a higher ability to present autoepitopes [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…The associations between HLA alleles predicted to bind to epitopes of the protein encoded by the BNT-162b2 vaccine and human disease were screened on the HLA-SPREAD platform (https://hla-spread.igib.res.in, accessed on 7 May 2023) [21]. The HLA-SPREAD platform consists of a huge database that collects evidence from more than 28 million peer-reviewed articles published on MEDLINE.…”

Section: Hla-spread Analysismentioning

confidence: 99%

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

Talotta¹

2023

Microorganisms

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Background: After the start of the worldwide COVID-19 vaccination campaign, there were increased reports of autoimmune diseases occurring de novo after vaccination. This in silico analysis aimed to investigate the presence of protein epitopes encoded by the BNT-162b2 mRNA vaccine, one of the most widely administered COVID-19 vaccines, which could induce autoimmunity in predisposed individuals. Methods: The FASTA sequence of the protein encoded by the BNT-162b2 vaccine served as the key input to the Immune Epitope Database and Analysis Resource. Linear peptides with 90% BLAST homology were selected, and T-cell, B-cell, and MHC-ligand assays without MHC restriction were searched and analyzed. HLA disease associations were screened on the HLA-SPREAD platform by selecting only positive markers. Results: By 7 May 2023, a total of 5693 epitopes corresponding to 21 viral but also human proteins were found. The latter included CHL1, ENTPD1, MEAF6, SLC35G2, and ZFHX2. Importantly, some autoepitopes may be presented by HLA alleles positively associated with various immunological diseases. Conclusions: The protein product of the BNT-162b2 mRNA vaccine contains immunogenic epitopes that may trigger autoimmune phenomena in predisposed individuals through a molecular mimicry mechanism. Genotyping for HLA alleles may help identify individuals at risk. However, further wet-lab studies are needed to confirm this hypothesis.

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HLA-SPREAD: a natural language processing based resource for curating HLA association from PubMed abstracts

Cited by 8 publications

References 40 publications

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing

Profiling the peripheral immune response to ex vivo TNF stimulation in untreated juvenile idiopathic arthritis using single cell RNA sequencing

HLA allele-calling using multi-ancestry whole-exome sequencing from the UK Biobank identifies 129 novel associations in 11 autoimmune diseases

Molecular Mimicry and HLA Polymorphisms May Drive Autoimmunity in Recipients of the BNT-162b2 mRNA Vaccine: A Computational Analysis

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