gMendel abstract for the ICHG, International Conference of Human Genetics in Cape Town, February 22-26, 2023

A software platform for real-time and automated simultaneous analysis and detection of genetic diseases

Eight out of ten rare diseases have a genetic cause. Often, they are chronic and life-threatening, and it takes seven years on average to receive an accurate diagnosis. Because of that, we
developed Phivea®, a software platform for real-time and automated simultaneous analysis and detection of genetic diseases using Oxford Nanopore Technologies (ONT). It enables extensive
numerical and visualization analysis and accurate, systematic and timely diagnosis significantly improving disease management.

The Phivea® platform analyzes the .fastq files generated by GridION x5 (ONT) and accesses them using a shared file system. The analysis process includes four phases:

1. Quality check (read length 900-1200bp with average Phred quality score above 8)
2. Demultiplexing (this is done using Tochlex, a method for real-time demultiplexing ONT
3. Chromosome classification (BLAST algorithm is used to compare the sequence with a
library and find the sequence characteristic specific for a particular chromosome)
4. Genetic disease classification and analysis report generation (Phivea® performs
discriminant analysis of the patients’ samples compared to controls and calculates the
probability of presence of genetic disorder)

The Phivea® platform can be applied directly on the stream of base-called DNA reads generated by the ONT device. It exceeds the limits of the real-time monitoring and analysis per DNA sample, which can significantly reduce the overall costs. The calculated throughput of the analysis pipeline is 4120 reads/s measured on a referent hardware architecture using thread parallelism of 10. Also, the current version of the Phivea® platform managed to correctly identify 6 different genetic disorders (Klinefelter, Turner, Down, Edwards, Patau and Prader-Willi/Angelman syndromes) with sensitivity and specificity higher than 90% on a patient level. Our technology was tested and validated on a mix of real and synthetically prepared samples, but the obtained results can be directly extrapolated for analysis and detection of other genetic disorders.

Authors & Affiliations:
Chris Kyriakidis1, M. Carmen Garrido Navas2,3,4,David Galevski5,6, Aleksandar Nikov6, Anne
Kristine Schack1,7, Lukasz Krych7, Zoran Velkoski1, Gjorgji Madjarov1,5,6

1 gMendel, Fruebjergvej 3, 2100 Copenhagen, Denmark
2 GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada,
Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, PTS Granada,
Granada, Spain
3 Genetics Department, Faculty of Sciences, Universidad de Granada, Granada, Spain.
4 CONGEN, Genetic Counselling Services, C/Albahaca 4, Granada, Spain
5 University Ss Cyril & Methodius, Skopje 1000, N. Macedonia
6 Netcetera, Zypressenstrasse 71, 8040 Zürich, Switzerland
7 University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg, Denmark

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