Inhibitory KIR ligands are associated with higher<i>P. falciparum</i>parasite prevalence

Digitale, Jean; Callaway, Perri C.; Martin, Maureen P.; Nelson, George W.; Viard, Mathias; Rek, John; Arinaitwe, Emmanuel; Dorsey, Grant; Kamya, Moses R.; Carrington, Mary; Rodríguez-Barraquer, Isabel; Feeney, Margaret E.

doi:10.1101/2020.04.04.20053504

Cited by 2 publications

(1 citation statement)

References 53 publications

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“…The KIR3DS1 allotypes are activating receptors, specific for non-polymorphic HLA-F and a smaller subset of HLA-A and -B [7][8][9]. Sequence diversity of KIR3DL1/S1 and HLA class I allotypes diversifies human immune responses to specific infections, cancers, cancer treatment and transplantation [10][11][12][13][14][15][16][17][18][19]. Accordingly, this genetically determined diversity also associates with differential susceptibility and severity for multiple immune-mediated diseases [20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1

Harrison

Leaton

Harrison³

et al. 2022

PLoS Comput Biol

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Highly polymorphic interaction of KIR3DL1 and KIR3DS1 with HLA class I ligands modulates the effector functions of natural killer (NK) cells and some T cells. This genetically determined diversity affects severity of infections, immune-mediated diseases, and some cancers, and impacts the course of immunotherapies, including transplantation. KIR3DL1 is an inhibitory receptor, and KIR3DS1 is an activating receptor encoded by the KIR3DL1/S1 gene that has more than 200 diverse and divergent alleles. Determination of KIR3DL1/S1 genotypes for medical application is hampered by complex sequence and structural variation, requiring targeted approaches to generate and analyze high-resolution allele data. To overcome these obstacles, we developed and optimized a model for imputing KIR3DL1/S1 alleles at high-resolution from whole-genome SNP data. We designed the model to represent a substantial component of human genetic diversity. Our Global imputation model is effective at genotyping KIR3DL1/S1 alleles with an accuracy ranging from 88% in Africans to 97% in East Asians, with mean specificity of 99% and sensitivity of 95% for alleles >1% frequency. We used the established algorithm of the HIBAG program, in a modification named Pulling Out Natural killer cell Genomics (PONG). Because HIBAG was designed to impute HLA alleles also from whole-genome SNP data, PONG allows combinatorial diversity of KIR3DL1/S1 with HLA-A and -B to be analyzed using complementary techniques on a single data source. The use of PONG thus negates the need for targeted sequencing data in very large-scale association studies where such methods might not be tractable.

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Section: Introductionmentioning

confidence: 99%

Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1

Harrison

Leaton

Harrison³

et al. 2022

PLoS Comput Biol

View full text Add to dashboard Cite

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Allele imputation for the Killer cell Immunoglobulin-like Receptor KIR3DL1/S1

Leaton

Ea³

et al. 2021

Preprint

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Highly polymorphic interactions of KIR3DL1 and KIR3DS1 with HLA class I ligands modulates the effector functions of natural killer (NK) cells and some T cells. This genetically determined diversity affects severity of infections, immune-mediated diseases, and some cancers, and impacts the course of cancer treatment, including transplantation. KIR3DL1 is an inhibitory receptor, and KIR3DS1 is an activating receptor encoded by the KIR3DL1/S1 gene that has more than 200 diverse and divergent alleles. Determination of KIR3DL1/S1 genotypes for medical application is hampered by complex sequence and structural variation that distinguishes individuals and populations, requiring targeted approaches to generate and analyze high-resolution allele data. To overcome these obstacles, we developed and optimized a model for imputing KIR3DL1/S1 alleles at high-resolution from whole-genome SNP data, and designed to represent a substantial component of human genetic diversity. We show that our Global model is effective at imputing KIR3DL1/S1 alleles with an accuracy ranging from 89% in Africans to 97% in East Asians, with mean specificity of 99.8% and sensitivity of 99% for named alleles >1% frequency. We used the established algorithm of the HIBAG program, in a modification named Pulling Out Natural killer cell Genomics (PONG). Because HIBAG was designed to impute HLA alleles also from whole-genome SNP data, PONG allows combinatorial diversity of KIR3DL1/S1 and HLA-A and B to be analyzed using complementary techniques on a single data source. The use of PONG thus negates the need for targeted sequencing data in very large-scale association studies where such methods might not be tractable. All code, imputation models, test data and documentation are available at https://github.com/NormanLabUCD/PONG.

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Inhibitory KIR ligands are associated with higherP. falciparumparasite prevalence

Cited by 2 publications

References 53 publications

Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1

Allele imputation for the killer cell immunoglobulin-like receptor KIR3DL1/S1

Allele imputation for the Killer cell Immunoglobulin-like Receptor KIR3DL1/S1

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