The Foundation of Trust in Precision Oncology
A genomic profiling assay is only as good as its validation. For oncologists to trust a test with life-altering treatment decisions, its sensitivity, specificity, reproducibility, and limits of detection must be rigorously established; not just claimed.
This study represents 1Cell.ai’s comprehensive clinical and technical validation of the OncoIndx® NGS platform, benchmarked against industry-standard reference materials, real patient samples, and FDA-approved cross-laboratory tests; establishing OncoIndx® as a reliable, high-precision tool for pan-cancer genomic profiling.
What OncoIndx® Profiles
OncoIndx® is a hybridization capture-based NGS assay targeting all exons and selected introns of 1080 cancer-related genes– covering 15,719 exonic regions, 339 intronic regions, and 50 gene fusions across 138 fusion partners.
In a single test, it detects single nucleotide variants (SNVs), copy number alterations (CNAs), structural variants, gene fusions, microsatellite instability (MSI), tumour mutational burden (TMB), homologous recombination deficiency (HRD), genome-wide loss of heterozygosity (gLOH), and 36 pharmacogenomic markers; compatible with both liquid and tissue biopsy samples.
Three Levels of Validation
The study employed a rigorous three-level validation framework across 63 samples:
Level 1– Reference Standards: 43 Seraseq™ NGS reference materials with known true mutations were tested across six tumour fractions from 0.1% to 5% VAF, assessing SNVs, INDELs, CNAs, and fusions across five sequential sequencing batches.
Level 2 – Clinical Samples: 14 patient samples were tested for concordance against clinically established hotspot findings across five key oncogenes- EGFR, ALK, KRAS, PIK3CA, and BRCA2.
Level 3 –Orthogonal Validation: MSI and TMB were validated against FDA-approved companion diagnostic tests from accredited cross-laboratory reference samples, and TMB was further benchmarked against TCGA whole-exome sequencing data.
Results That Establish Clinical Confidence
The performance of OncoIndx® across all variant classes was exceptional:
• 100% sensitivity, specificity, PPV and NPV for SNVs at 5% VAF, with zero false positives even at 1% VAF
100% accuracy for CNAs with no false positives or false negatives
• 98.48% accuracy for gene fusions with 100% specificity
• 97.40% accuracy for small INDELs with 100% specificity
• Detection of variants at VAFs as low as 0.1%, with 83% of SNVs and 60% of INDELs detectable below 1% VAF
• 100% concordance for EGFR, ALK, KRAS, and BRCA2 in clinical samples
• MSI detected with 95% accuracy, 90% sensitivity, and 100% specificity against FDA-approved reference tests
TMB validated with a Pearson correlation of r = 0.9885 against TCGA whole-exome sequencing data
All variant calling and annotation was performed through the iCare™ platform– 1Cell.ai’s proprietary cloud-based bioinformatics system that streamlines the entire post-sequencing workflow from raw FASTQ input to fully annotated clinical report.
Why This Matters
Comprehensive genomic profiling is only transformative when clinicians can trust what it tells them. This validation study conducted using established international guidelines from the Association for Molecular Pathology, ASCO, and the College of American Pathologists – provides that foundation of trust for OncoIndx®.
With proven performance across SNVs, CNAs, fusions, and complex biomarkers at tumour fractions as low as 0.1%, OncoIndx® is validated to detect what smaller panels miss, at the sensitivity levels precision oncology demands.
This is the assay behind more than 4,000 clinical samples profiled to date and the data that confirms it is ready for the rigour of real-world oncology practice.
Published in Cancers (Basel) | Volume 16, Issue 19 | October 2024 | Open Access via PubMed Central
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