Long Read Sequencing for Pharmacogenomics

Pharmacogenomics (PGx) guided drug therapy is one of the cornerstones of personalized medicine. However, the genes involved in drug response are complex and known to harbor many (rare) variants. Short-read sequencing and SNP panels have limited ability to resolve these genes and characterize all variants. CD Genomics is a leading global life sciences company providing specialized long-read sequencing solutions for pharmacogenomics research. We aim to characterize complex genomic regions associated with drug response to help personalized medicine research develop therapeutic management tailored to an individual's genetic makeup.

Introduction to Pharmacogenomics

Pharmacogenomics (PGx) uses genomic information to assess an individual's response to certain drugs and is essential for individualizing drug dosing to improve drug treatment outcomes. PGx relies on inferred phenotypes based on known variants in pharmacogenetic genes. However, due to the complex genetic composition of most pharmacogenetic genes, which are at least partially located in complex genomic regions or contain variants such as tandem repeats and pseudogene heterozygous conformations, it is currently not possible to account for all of the genetic variations. It is therefore important to be able to explain all of the genetic components that drive variable drug responses in order to assess which parts of variability are inherited and which parts can be explained by other factors. Single nucleotide variant (SNV) based microarrays and short-read sequencing do not adequately and reliably resolve highly homologous regions and identify PGx variants. In addition, these technologies do not always allow for stereotypic variation of their originating alleles. Recent advances in long-read sequencing technologies show promise in addressing these issues.

Fig. 1. Haploblock resolution of GENCODE features. (van der Lee et al., 2022)

Solutions Offering at CD Genomics

Our advanced long read sequencing platforms, PacBio SMRT sequencing and ONT Nanopore sequencing are capable of characterizing complex pharmacogenomic regions. CD Genomics is committed to delivering highly accurate long read sequencing to achieve high-resolution insights into PGx loci, which include pseudogenes, tandem repeat sequences, and complex variants such as CNVs. Our long read HiFi sequencing solutions accurately detect structural and complex variants, direct haplotype phasing, and coverage of rare variants compared to other technologies.

Our long read sequencing solutions for pharmacogenomics include:

• Characterization of Complex Pharmacogenetic Genes

Our long read sequencing solutions can comprehensively characterize complex pharmacogenetic genes. Variant identification accuracy is achieved by generating long and high-quality reads and allows for full stereotypic diplotype resolution. The ability to resolve complex regions helps researchers more accurately understand the genetic components that drive variable drug responses.

• Accurate Variant Calling

In pharmacogenomics, the accuracy of variant recognition is critical for identifying genetic variants that influence drug response. Our long read sequencing has high accuracy in pharmacogenetic variant calling, ensuring 99.8% recall and 100% precision for single nucleotide variants (SNVs) and 98.7% precision and 98.0% recall for insertions and deletions (Indels).

• Analysis of Gene-Drug Interactions

Our long read sequencing helps you gain a more complete understanding of gene-drug interactions by improving the resolution of the genes involved. This increased resolution enables clinicians to make more informed decisions about drug therapy based on an individual's genetic profile.

• Haplotype Profiling

Haplotype phasing, which determines the arrangement of genetic variants on an individual's chromosomes, is important for understanding the functional consequences of pharmacogenomic variation. Our long read sequencing solutions provide direct information about haplotypes without the need for computational methods or genealogical information. Accurate haplotype phasing achieved by long read sequencing can improve the accuracy of phenotype prediction in pharmacogenomics. It allows for a finer-grained assessment of drug metabolism phenotypes, which enhances the individualization of drug dosing.

Advantages of Our Long Read Sequencing Solutions for Pharmacogenomics

• A simplified end-to-end workflow enables more accurate detection of highly polymorphic pharmacogenomics genes.
• With read lengths up to 25 kb and accuracy >99.9%, HiFi sequencing supports PGx discovery and translational research, helping to drive personalized medicine and potentially improve patient care.
• Amplicon-based HiFi sequencing completely and directly resolves and phases complex motifs (e.g., CYP2D6) without assembly or inference, enabling ancestry-independent haplotype assignment.
• Multiple bioinformatics tools for secondary and tertiary analysis.

CD Genomics is committed to providing accurate, comprehensive, and high-resolution long read sequencing solutions to accelerate pharmacogenomics research. Characterizing complex pharmacogenomic regions helps advance personalized medicine and optimize drug therapy outcomes. If you have any questions, please feel free to contact us. We look forward to working with you on projects of interest.

Related Services

PacBio SMRT Sequencing
Oxford Nanopore Sequencing
Human Whole Genome Sequencing
Human Genome Structural Variation Detection
Pacbio RNA Sequencing
Nanopore RNA Sequencing