Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios

Maria Luisa Matey-Hernandez; Danish Pan Genome Consortium; Søren Brunak; Jose M.G. Izarzugaza; Lasse Maretty Sørensen; Bent Petersen; Jonas Andreas Sibbesen; Siyang Liu; Kirstine G Belling; Christian Theil Have; Jette Bork-Jensen; Jihua Sun; Torben Hansen; Anders Krogh; Thorkild I.A. Sørensen; Oluf Borbye Pedersen; Jun Wang; Hans Rudolf Lytchoff Eiberg; Karsten Kristiansen

doi:10.1186/s12859-018-2239-6

Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios

Maria Luisa Matey-Hernandez, Danish Pan Genome Consortium, Søren Brunak, Jose M.G. Izarzugaza, Lasse Maretty Sørensen, Bent Petersen, Jonas Andreas Sibbesen, Siyang Liu, Kirstine G Belling, Christian Theil Have, Jette Bork-Jensen, Jihua Sun, Torben Hansen, Anders Krogh, Thorkild I.A. Sørensen, Oluf Borbye Pedersen, Jun Wang, Hans Rudolf Lytchoff Eiberg, Karsten Kristiansen

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Abstract

BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.

RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles.

CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential.

Original language	English
Article number	239
Journal	BMC Bioinformatics
Volume	19
Pages (from-to)	1-12
ISSN	1471-2105
DOIs	https://doi.org/10.1186/s12859-018-2239-6
Publication status	Published - 2018

Keywords

Clinical genomics
HLA genotyping
NGS
Population genetics
Prediction

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental triosFinal published version, 0.98 MBLicence: CC BY

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Matey-Hernandez, M. L., Danish Pan Genome Consortium, Brunak, S., Izarzugaza, J. M. G., Sørensen, L. M., Petersen, B., Sibbesen, J. A., Liu, S., Belling, K. G., Have, C. T., Bork-Jensen, J., Sun, J., Hansen, T., Krogh, A., Sørensen, T. I. A., Pedersen, O. B., Wang, J., Eiberg, H. R. L., & Kristiansen, K. (2018). Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios. BMC Bioinformatics, 19, 1-12. Article 239. https://doi.org/10.1186/s12859-018-2239-6

Matey-Hernandez, ML, Danish Pan Genome Consortium, Brunak, S, Izarzugaza, JMG, Sørensen, LM, Petersen, B , Sibbesen, JA, Liu, S, Belling, KG, Have, CT, Bork-Jensen, J, Sun, J, Hansen, T , Krogh, A , Sørensen, TIA , Pedersen, OB, Wang, J, Eiberg, HRL & Kristiansen, K 2018, 'Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios', BMC Bioinformatics, vol. 19, 239, pp. 1-12. https://doi.org/10.1186/s12859-018-2239-6

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title = "Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios",

abstract = "BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles.CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential.",

keywords = "Clinical genomics, HLA genotyping, NGS, Population genetics, Prediction",

author = "Matey-Hernandez, {Maria Luisa} and {Danish Pan Genome Consortium} and S{\o}ren Brunak and Izarzugaza, {Jose M.G.} and S{\o}rensen, {Lasse Maretty} and Bent Petersen and Sibbesen, {Jonas Andreas} and Siyang Liu and Belling, {Kirstine G} and Have, {Christian Theil} and Jette Bork-Jensen and Jihua Sun and Torben Hansen and Anders Krogh and S{\o}rensen, {Thorkild I.A.} and Pedersen, {Oluf Borbye} and Jun Wang and Eiberg, {Hans Rudolf Lytchoff} and Karsten Kristiansen",

year = "2018",

doi = "10.1186/s12859-018-2239-6",

language = "English",

volume = "19",

pages = "1--12",

journal = "BMC Bioinformatics",

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T1 - Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios

AU - Matey-Hernandez, Maria Luisa

AU - Danish Pan Genome Consortium

AU - Brunak, Søren

AU - Izarzugaza, Jose M.G.

AU - Sørensen, Lasse Maretty

AU - Petersen, Bent

AU - Sibbesen, Jonas Andreas

AU - Liu, Siyang

AU - Belling, Kirstine G

AU - Have, Christian Theil

AU - Bork-Jensen, Jette

AU - Sun, Jihua

AU - Hansen, Torben

AU - Krogh, Anders

AU - Sørensen, Thorkild I.A.

AU - Pedersen, Oluf Borbye

AU - Wang, Jun

AU - Eiberg, Hans Rudolf Lytchoff

AU - Kristiansen, Karsten

PY - 2018

Y1 - 2018

N2 - BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles.CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential.

AB - BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles.CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential.

KW - Clinical genomics

KW - HLA genotyping

KW - NGS

KW - Population genetics

KW - Prediction

U2 - 10.1186/s12859-018-2239-6

DO - 10.1186/s12859-018-2239-6

M3 - Journal article

C2 - 29940840

SN - 1471-2105

VL - 19

SP - 1

EP - 12

JO - BMC Bioinformatics

JF - BMC Bioinformatics

M1 - 239

ER -

Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios

Abstract

Keywords

UN SDGs

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