Development of the OncoSignal Algorithm for Detecting Low Abundance Circulating Tumor DNA Signals Compared with Conventional Threshold Based and Machine Learning Detection
Abstract
Circulating tumor DNA (ctDNA) provides a minimally invasive molecular signal for cancer detection, residual disease assessment, treatment-response monitoring, and recurrence surveillance; however, reliable identification becomes difficult when tumor-derived fragments occur at very low variant allele fractions within a dominant background of normal cell-free DNA. This study develops OncoSignal, a novel computational algorithm for detecting low-abundance ctDNA through integrated background-error modelling, fragment-level signal weighting, molecular-context encoding, adaptive denoising, probabilistic evidence fusion, and confidence-calibrated classification. Unlike conventional fixed-threshold approaches that classify candidate variants primarily according to read depth, allele frequency, or predefined quality cut-offs, OncoSignal constructs a multidimensional evidence score from variant allele frequency, base quality, mapping quality, strand consistency, fragment length, genomic context, local sequencing error, molecular support, and locus-specific noise characteristics. The proposed architecture incorporates an Adaptive Molecular Noise Suppression module, Fragment-Context Attention Network, Bayesian Evidence Fusion layer, and Dynamic Signal Decision Boundary, allowing the detection threshold to adjust to sequencing depth, background error distribution, and sample-specific noise. OncoSignal is designed for comparative benchmarking against conventional variant allele frequency thresholding, statistical binomial detection, logistic regression, support vector machine, random forest, XGBoost, multilayer perceptron, one-dimensional convolutional neural networks, long short-term memory networks, and Transformer-based classifiers. Performance is evaluated across progressively decreasing ctDNA fractions using sensitivity, specificity, precision, F1-score, Matthews correlation coefficient, area under the receiver operating characteristic curve, area under the precision-recall curve, false-positive rate, calibration error, signal-to-noise ratio, and limit of detection. Particular emphasis is placed on the clinically demanding low-abundance interval below 1% variant allele frequency and the ultra-low range below 0.1%. Comparative graphical analysis includes ROC and precision-recall curves, sensitivity-versus-variant-allele-frequency profiles, three-dimensional surfaces relating sequencing depth, tumor fraction, and detection probability, calibration plots, signal-to-noise distributions, and error-rate comparisons across algorithms. The central hypothesis is that adaptive integration of molecular evidence and locus-specific background modelling will preserve true weak tumor signals while suppressing sequencing artefacts more effectively than fixed thresholds and conventional machine-learning classifiers. The resulting OncoSignal framework is intended to provide a more sensitive, specific, interpretable, and technically robust computational platform for low-abundance ctDNA detection and subsequent liquid-biopsy applications.
How to Cite This Article
Rukayat Olayemi Oni, Yewande Iyimide Adeyeye (2022). Development of the OncoSignal Algorithm for Detecting Low Abundance Circulating Tumor DNA Signals Compared with Conventional Threshold Based and Machine Learning Detection . International Journal of Medical and All Body Health Research (IJMABHR), 3(1), 87-103. DOI: https://doi.org/10.54660/IJMBHR.2022.3.1.87-103