Analytical and Clinical Validation of a Target-Enhanced Whole Genome Sequencing-Based Comprehensive Genomic Profiling Test

Figures & data

Table 1. Overall performance of target enhanced -whole genome sequencing (TE-WGS).

	Variant	Specification
Analytical Sensitivity	SNV	99.8% (CI 99.79–99.83)
	Indel	99.2% (CI 99.14–99.72)
Analytical PPV	SNV	99.3% (CI 99.28–99.38)
	Indel	98.7% (CI 98.63–98.78)

Indel: insertion, and deletion; PPV: positive predictive value; SNV: single nucleotide variant.

Figure 1. Correlation of expected and observed variant allele fractions in the reference material. Observed variant allele fraction single nucleotide variants (A) and insertion and deletion variants (B) by TE-WGS were concordant with the expected variant allele fractions provided by the reference material manufacturer.

Figure 2. (A) KRAS G12V reference standard serial dilution to assess the limit of detection (LOD). The minimum LOD for SNVs has been established at a VAF of 5%. (B) Violin plot depicting depth distribution across all targets in four analytical validation (AV) samples. Notably, the KRAS locus exhibits lower coverage (red dot), suggesting higher depth and potentially lower LOD (enhanced sensitivity) for most other targets. Black dots represent mean values, while horizontal lines indicate medians.

Table 2. Tumor types of the samples for clinical validation.

Tumor types	Number of samples (percent)
Breast cancer	12 (42.9%)
Stomach cancer	6 (21.4%)
Head and neck cancer	3 (10.7%)
Bladder cancer	2 (7.1%)
Gallbladder cancer	2 (7.1%)
Lung cancer	1 (3.6%)
Colorectal cancer	1 (3.6%)
Small bowel cancer	1 (3.6%)
Total	28 (100%)

Figure 3. Comparative Analysis of Copy Number and Variant Allele Frequency (VAF) in Tumor Samples. (A) Demonstrates a tumor characterized by widespread chromosomal arm-level and segmental copy number alterations, indicative of significant loss-of- heterozygosity and allelic imbalance. (B) Illustrates a sample with a low tumor cell fraction, revealing minimal copy number changes and allelic imbalance.

Data availability statement

The patients participating in this study did not consent to the public release of sequencing data. The TE-WGS pipeline and associated algorithms are proprietary to Inocras Inc.