Scientific research results | AlloDx's research article on the analysis of factors affecting the detection of donor-derived cell-free DNA is officially published

Recently, an important result of the AlloDx research team - Analysis of the primary factors influencing donor derived cell-free DNA testing in kidney transplantation (Analysis of the main factors influencing donor derived cell-free DNA testing in kidney transplantation), was included and published in the Allogeneic Immunity and Transplantation column of Frontiers in Immunology (DOI number: https://doi.org/10.3389/fimmu.2024.1435578).

At present, a growing number of domestic renal transplant clinical centers have begun to use donor-derived cell-free DNA (dd-cfDNA) testing technology. This novel non-invasive diagnostic technique brings sensitive and convenient post-transplant monitoring experience to kidney recipients. However, in actual dd-cfDNA use, many technical key points and clinical interpretation of results remain to be clarified. For example: distinguishing donor and recipient gene signals in body fluids is one of the important conditions for ensuring test result accuracy, and the choice of SNP number and sequencing depth require seeking a better balance between medical cost and clinical benefit. Then, how many SNP/Indel loci are actually needed to test dd-cfDNA? What is the correlation between sequencing depth and quantitative accuracy? In addition, what is the influence of renal nucleosome imprinting on dd-cfDNA cutoff values? Why do absolute and relative values often differ? What are the distribution patterns of blood and urine dd-cfDNA values under different renal injury pathologies? This study was among the earlier to systematically analyze these questions globally.

1. Equation for calculating the number of SNPs or Indels required to accurately distinguish donor and acceptor signals.

2. Correlation analysis between sequencing depth and dd-cfDNA detection error rate

Figure 3. (A) Minimum required sequencing depth and (B) relative errors for %dd-cfDNA.

3. The impact of kidney-specific nucleosome imprinting on the critical value of dd-cfDNA detection

4. Comparison of the advantages and disadvantages of relative and absolute values of dd-cfDNA

Table 1. Comparison of advantages and disadvantages between absolute and fraction values.

In short, the accuracy of methodological detection is the prerequisite for clinical use of dd-cfDNA. AlloDx took seven years to create Ankang AlloK seq based on 15,000+ samples.^®(liquid biopsy solution), with its independently developed ID-Tag technology, it can achieve high-precision detection of low-frequency mutations of one thousandth per thousand at ultra-high sequencing depth by enriching free DNA and reducing background noise interference. As more and more donor-derived cell-free DNA testing specifications are published, I believe that clinicians and kidney patients will have a more systematic and comprehensive understanding of this new transplant immune biomarker, and will be able to make choices that better suit their own needs when faced with various monitoring technologies after transplantation.