Off-Target-Based Tumor Fraction Estimation from Targeted Sequencing Shows Concordance with Orthogonal…

StudyInternational journal of molecular sciences· Jul 2026

Off-Target-Based Tumor Fraction Estimation from Targeted Sequencing Shows Concordance with Orthogonal Methods Across Advanced Solid Tumors.

Samantha O Hasenleithner, Shilpa Rao, Jian Q Yu … Sandra V Fernandez

Molecular Genetic PathologyStudyQ1IF 5.8

Fragle off-target tumor fraction estimates strongly correlate with low-pass whole-genome sequencing.

Off-Target-Based Tumor Fraction Estimation from Targeted Sequencing Shows Concordance with Orthogonal Methods Across Advanced Solid Tumors.

Samantha O Hasenleithner … Sandra V Fernandez

International journal of molecular sciences · Jul 2026 · Q1 in General Medicine

Background

Circulating tumor DNA fraction (ctFraction) has emerged as an important biomarker for assessing tumor burden and monitoring treatment response in patients with cancer.

Methods

In this study, we compared ctFraction estimates generated by ichorCNA, Fragle low-pass whole-genome sequencing (Fragle LP-WGS), Fragle off-target, and OTTER, a proprietary algorithm from Tempus AI.

n = 33 patients

Results

off-target Fragle results track closely with the low-pass sequencing method

0.903rho

Fragle off-target

0.698rho

OTTER

0.696rho

ichorCNA

More results

Mean VAF (mVAF) significantly correlated with all ctFraction estimates, with the strongest association observed for ichorCNA (rho = 0.910), followed by OTTER (rho = 0.865), Fragle LP-WGS (rho = 0.680), and Fragle off-target (rho = 0.658).

More results

Longitudinal analysis of 20 patients at baseline and after two cycles of treatment demonstrated strong correlations between changes in ctFraction (ΔctFraction) and mean ΔVAF for both ichorCNA and Fragle off-target (r = 0.955 and r = 0.906, respectively).

“

Conclusion

Larger prospective studies are warranted to further evaluate Fragle off-target clinical utility for treatment monitoring and outcome prediction.

Off-Target-Based Tumor Fraction Estimation from Targeted Sequencing Shows Concordance with Orthogonal Methods Across Advanced Solid Tumors.

Off-Target-Based Tumor Fraction Estimation from Targeted Sequencing Shows Concordance with Orthogonal Methods Across Advanced Solid Tumors.

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