Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis
Human leukocyte antigens (HLA) are important biomarkers since multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative an in situ synthesized DNA-based microarray...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00597/full |
| _version_ | 1818879450935197696 |
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| author | Vladimir eBrusic Vladimir eBrusic |
| author_facet | Vladimir eBrusic Vladimir eBrusic |
| author_sort | Vladimir eBrusic |
| collection | DOAJ |
| description | Human leukocyte antigens (HLA) are important biomarkers since multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative an in situ synthesized DNA-based microarray method that contains hundreds of thousands of probes representing a complete overlapping set covering 1,610 clinically relevant HLA class I alleles accompanied by computational tools for assigning HLA type to 4-digit resolution. Our proof-of-concept experiment included 21 blood samples, 18 cell lines, and multiple controls. The method is accurate, robust, and amenable to automation. Typing errors were restricted to homozygous samples or those with very closely related alleles from the same locus, but readily resolved by targeted DNA sequencing validation of flagged samples. High-throughput HLA typing technologies that are effective, yet inexpensive, can be used to analyze the world’s populations, benefiting both global public health and personalized health care. |
| first_indexed | 2024-12-19T14:30:16Z |
| format | Article |
| id | doaj.art-76ce510b83d24fc68aaee70d87d62358 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T14:30:16Z |
| publishDate | 2014-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-76ce510b83d24fc68aaee70d87d623582022-12-21T20:17:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242014-11-01510.3389/fimmu.2014.00597109693Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array AnalysisVladimir eBrusic0Vladimir eBrusic1Dana-Farber Cancer InstituteBoston UniversityHuman leukocyte antigens (HLA) are important biomarkers since multiple diseases, drug toxicity, and vaccine responses reveal strong HLA associations. Current clinical HLA typing is an elimination process requiring serial testing. We present an alternative an in situ synthesized DNA-based microarray method that contains hundreds of thousands of probes representing a complete overlapping set covering 1,610 clinically relevant HLA class I alleles accompanied by computational tools for assigning HLA type to 4-digit resolution. Our proof-of-concept experiment included 21 blood samples, 18 cell lines, and multiple controls. The method is accurate, robust, and amenable to automation. Typing errors were restricted to homozygous samples or those with very closely related alleles from the same locus, but readily resolved by targeted DNA sequencing validation of flagged samples. High-throughput HLA typing technologies that are effective, yet inexpensive, can be used to analyze the world’s populations, benefiting both global public health and personalized health care.http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00597/fullHigh-Throughput Screening Assaysmachine learningHLA typingHLA disease associationpopulation typing |
| spellingShingle | Vladimir eBrusic Vladimir eBrusic Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis Frontiers in Immunology High-Throughput Screening Assays machine learning HLA typing HLA disease association population typing |
| title | Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis |
| title_full | Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis |
| title_fullStr | Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis |
| title_full_unstemmed | Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis |
| title_short | Human Leukocyte Antigen Typing Using a Knowledge Base Coupled with a High Throughput Oligonucleotide Probe Array Analysis |
| title_sort | human leukocyte antigen typing using a knowledge base coupled with a high throughput oligonucleotide probe array analysis |
| topic | High-Throughput Screening Assays machine learning HLA typing HLA disease association population typing |
| url | http://journal.frontiersin.org/Journal/10.3389/fimmu.2014.00597/full |
| work_keys_str_mv | AT vladimirebrusic humanleukocyteantigentypingusingaknowledgebasecoupledwithahighthroughputoligonucleotideprobearrayanalysis AT vladimirebrusic humanleukocyteantigentypingusingaknowledgebasecoupledwithahighthroughputoligonucleotideprobearrayanalysis |