Microarray Research Solutions for Extended Blood Typing

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A universal DNA-based solution to enable comprehensive, cost-effective blood genotyping for extended and rare blood types

Blood typing is a medical service used to match patients who need blood transfusions with donor blood. When a patient receives a transfusion that doesn’t precisely match their blood type, it can increase the risk of adverse reactions including hemolytic complications in future transfusions.

 

Classifying blood into one of four major types (A, B, AB, and O) and determining the RhD positive or negative type has been the standard for blood typing, but modern medicine recognizes many more additional minor blood types that are relevant for patients especially those in need of frequent transfusions. With the help of Thermo Fisher Scientific, blood service centers can test for extended and rare blood types without the need for multiple tests, enabling them to scale precision blood typing research to improve and expand the critical service of blood type matching.

Whitepaper: Genotyping for extended and rare blood types

This informative whitepaper highlights various challenges with conventional blood typing and elaborates on the ways to improve. It answers health groups’ calls for more precise blood genotyping with the Axiom BloodGenomiX Array.

BloodGenomiX Array

The Applied Biosystems Axiom BloodGenomiX Array is a high throughput solution for more precise blood group genotyping research at scale. Blood service centers can detect most extended and rare blood groups and tissue (HLA) and platelet (HPA) types in a single assay, eliminating the need for expensive, time consuming, and multiple conventional blood typing research methods. Blood typing is a critical medical service and this technology, developed in conjunction with leading international blood transfusion services experts, aims to improve research in donor blood matching to promote improved outcomes and make transfusions safer. With minimal hands-on time and training, blood product providers will be able to effectively optimize blood matching with this DNA-based research solution. The Axiom BloodGenomiX Array coupled with BloodGenomiX Reporter Software provides an end-to-end workflow and reporting output.

Targeted yet comprehensive content for blood research needs related to transfusion

  • Comprehensive coverage with nearly 20,000 probe-variant pairs, meticulously designed to cater to genetic variations in blood group system, HLA, and HPA genes relevant for transfusion therapy
  • Excellent coverage for European, African, admixed American, East Asian, and South Asian populations
  • Human erythrocyte antigen (HEA) variants in 38 blood group systems, providing valuable information for finding rare or uncommon donors for clinical research
  • Human platelet antigens (HPAs) and human neutrophil antigens (HNAs), targeting the most important antigens identified by global blood experts
  • Human leukocyte antigen (HLA) typing, covering the HLA class I genes relevant for transfusion therapy
  • Interrogation of variants related to Hemoglobin S and C disorders
  • Extensive coverage of iron regulation, specifically addressing hereditary hemochromatosis and helping provide research insights related to iron-deficiency anemia in donors
  • Examination of donor characteristics, including restless leg syndrome, enabling researchers to have a holistic understanding of donor health profiles
  • Evaluation of variants potentially associated with product quality related to potassium leakage, hemolysis, and storage stability

Outstanding coverage to determine human erythrocyte antigen (HEA) types

The Axiom BloodGenomiX Array includes nearly 400 probesets meticulously selected  to interrogate 261 antigens across 38 blood group systems in addition to multiple HPA and HNA types. The variants underlying HEA types are divided into two categories: 1) core variants (Table 1) for which samples from at least five unrelated individuals have been typed as homozygous for the uncommon or rare allele and 2) Research Screen variants, which include low frequency variants where fewer than five individuals homozygous for the uncommon or rare allele have been typed in the external validation study performed by the Blood transfusion Genomics Consortium (www.bgc.io).

 

System number

Blood group (HEA) system

Gene

Antigen

2

MNS

GYPA

M, N

2 MNS GYPB S, s, U

2

MNS

GYPB

GYPB*05N (U–)

2

MNS

GYPB

GYPB*NY (U+w) 

2

MNS

GYPB

GYPB*P2 (U+w)  

4

RH

RHD

D-, partial C+ [RHD*03N.01]

4

RH

RHCE

C, c, E, e, C(W)

C(X), V, VS 

5

LU

BCAM

Lu(a), Lu(b)

6

KEL

KEL

K, k, Kp(a), Kp(b)

Js(a), Js(b) 

8

FY

ACKR1

Fy(a), Fy(b)

8

FY

ACKR1

FY*02N.01 (Fyb null) 

8

FY

ACKR1

FY*02W.01 (Fy(b+w)) 

9

JK

SLC14A1

Jk(a),  Jk(b) 

9

JK

SLC14A1

JK*01W.01 (Jk(a+w))

9

JK

SLC14A1

JK*02N.01 (Jkb null)

9

JK

SLC14A1

JK*02N.06 (Jkb null)

10

DI

SLC4A1

Di(a), Di(b), Wr(a), Wr(b)

11

YT

ACHE

Yt(a), Yt(b)

13

SC

ERMAP

Sc1, Sc2

14

DO

ART4

Do(a), Do(b), Hy, Jo(a)

15

CO

AQP1

Co(a), Co(b)

16

LW

ICAM4

LW(a), Lw(b)

21

CROM

CD55

Cr(a)

22

KN

CR1

KCAM, KDAS

Kn(a), Kn(b)

McC(a), McC(b), Yk(a)

34

VEL

SMIM1

Vel

 

Table 1: Core variant coverage with BloodGenomiX Reporter Software

Copy number-aware genotyping to enhance accuracy in duplicated genes

Deletions of genes or exons, such as seen with RHD, present challenges in accurately calling genotypes of RHD variants and variants in the related RHCE gene which has a very similar sequence. For genes with frequent deletions like RHD, the Axiom BloodGenomiX Array uses copy number aware genotyping (CNAG) to call variants using a diploid model for samples with two copies of RHD, a haploid model for samples with a single copy of RHD, and an automatic result of not present for samples with no copies. In the closely related RHCE gene, probes for RHCE variants receive variable amounts of background signal relative to copy number changes in RHD. The Axiom BloodGenomiX Array uses remote copy number aware genotyping (“Remote”) to call RHCE variants in samples partitioned according to their number of copies of the RHD gene. These algorithms increase accuracy for genes that have been previously difficult to call correctly. Similar approaches are used for calling variants and detecting deletions in the GYPB gene, which are causal of the U-negative phenotype if present in homozygosity, and mainly found in individuals of African and Admixed American ancestry.

 

Comprehensive content for blood research also available for population scale research studies

For researchers wanting to add blood typing information to their larger population scale studies, the Axiom PangenomiX Array combines all the valuable genotyping information available on the BloodGenomiX array with the largest population coverage on a high-throughput array. The Axiom PangenomiX Array is a valuable research tool for human genomics, including applications such as genome-wide association studies (GWAS), population health initiatives, polygenic risk score research and development, and clinical research for trials in drug discovery. 

Customization to meet you where you are—Axiom MyDesign arrays

Not seeing the content you’re looking for? Thermo Fisher Scientific has bioinformaticians with years of custom design and genotyping analysis expertise who can work with you to bring a custom designed array to life. Include markers of your choosing or select markers from the Axiom Genomic Database, which contains over 11 million high-performance genotypes.


Axiom Propel XPRES workflow

The Applied Biosystems Axiom Propel XPRES 2x384HT workflow, widely used in laboratories across the globe for Axiom genotyping research applications, empowers you to disrupt the bottleneck in scaling-up genotyping by eliminating the need for high upfront capital investment for automated liquid handlers. It is a new, innovative workflow utilizing versatile, easy-to-use Thermo Scientific Multidrop Combi liquid dispensers and other common laboratory equipment for Axiom target preparation without changing the existing steps. The Axiom Propel XPRES 2x384HT workflow offers a scalable, modular, high-throughput and cost-effective DNA-based blood genotyping research solution for Axiom BloodGenomiX applications.


Microarray analysis instrument for blood typing research

GeneTitan MC Fast Scan Instrument

The GeneTitan MC Fast Scan Instrument and proven Axiom array plates in 96- and 384-array layouts provide a highly automated solution for genome-wide SNP genotyping.

 

The GeneTitan MC Fast Scan Instrument automates array processing from target hybridization to data generation by combining a hybridization oven, fluidics processing, and a state-of-the art imaging device into a single bench-top instrument.

 

The imaging device in the GeneTitan MC Fast Scan Instrument uses an external, high-intensity xenon lamp and dual excitation and emission filters to capture images from array plates for use in expression, genotyping, and microbiome studies.

Key benefits include:

  • Fast—condenses hands-on processing time to as little as 30 minutes, images an array in less than five minutes, and operates unattended overnight
  • Scalable—meets both medium- and high-throughput needs, enables fast time to data, and requires minimal manual intervention
  • Flexible—supports genotyping studies on multiple array plate formats
  • Accurate—enables high-quality, consistent data by processing multiple samples under identical conditions
  • Adaptable—creates flexible workflows and sample registration via GeneChip Command Console Software

Software

Automated Axiom Analysis Software

Applied Biosystems Automated Axiom Analysis Software enables walk-away capability for laboratory professionals and bioinformaticians who are routinely analyzing microarray data. This easy-to-use data analysis tool allows microarray analysis to run automatically. Following the run, CEL and ARR files are automatically uploaded to the Automated Axiom Analysis Software for sample analysis. Users can then view batch analysis status, analysis summaries by batch, as well as sample QC per plate. In addition, users can monitor summarized marker metrics at a time of their choosing.

Benefits of Automated Axiom Analysis Software

Automated Axiom Analysis Software seeks to address efficiency issues by enabling laboratories to continually process microarray samples . Results can be viewed at a time of the user’s choosing. Automated Axiom Analysis Software improves data analysis efficiency  via a streamlined data analysis workflow and automated report formatting and export.

BloodGenomiX Reporter Software and human leukocyte antigen (HLA) imputation

Integrated seamlessly into the Automated Axiom Analysis Software, the BloodGenomiX Reporter Software transforms genotyping data output from the GeneTitan instrument into HEA, HNA, and HPA phenotypes after performing  quality control to identify samples with evidence of contamination, with such samples removed from further analysis. For each tested sample, the BloodGenomiX Reporter Software determines HEA, HNA and HPA types by directly interrogating relevant DNA variants associated with antigen expression. This is done in accordance with the global standards established by the International Society of Blood Transfusion (ISBT). The embedded HLA software then employs imputation on the genotyping results to predict HLA Class I antigen types against a globally maintained database of known reference haplotypes.

 

The final output flat file from BloodGenomiX Reporter Software has been formatted with direct feedback from blood blanks to allow for easier integration into electronic health records such as eProgesa or HEMATOS. The integration of Automated Axiom Analysis and BloodGenomiX Reporter softwares offers a comprehensive solution for streamlined microarray analysis, facilitating precision in antigen typing and HLA imputation. The user-friendly interface and adherence to global standards contribute to efficient and accurate genomics analysis in genomics analysis in blood transfusion research.

GeneChip Command Console Software

GeneChip Command Console Software supports customization, automation, and integration flexibility along with full-range support:

  • Provides summary of probe cell intensity data (CEL file generation); enables sample and array registration, data management, instrument control, and automatic and manual image gridding
  • Enables flexiblility to customize, automate, and integrate workflows with a variety of laboratory information management systems
  • Supports the full range of RUO assays

Ordering information

Contact us today to learn more about extended blood typing.