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<journal-meta>
<journal-id journal-id-type="publisher-id">IJMABHR</journal-id>
<journal-title-group><journal-title>International Journal of Medical and All Body Health Research</journal-title><abbrev-journal-title>IJMABHR</abbrev-journal-title></journal-title-group>
<issn pub-type="epub">2582-8940</issn>
<publisher><publisher-name>Anfo Publication House</publisher-name></publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">548</article-id>
<article-id pub-id-type="doi">10.54660/IJMBHR.2022.3.1.87-103</article-id>
<title-group><article-title>Development of the OncoSignal Algorithm for Detecting Low Abundance Circulating Tumor DNA Signals Compared with Conventional Threshold Based and Machine Learning Detection</article-title></title-group>
<contrib-group>
<contrib contrib-type="author"><name><surname>Oni</surname><given-names>Rukayat Olayemi</given-names></name></contrib>
<contrib contrib-type="author"><name><surname>Adeyeye</surname><given-names>Yewande Iyimide</given-names></name></contrib>
</contrib-group>
<pub-date publication-format="electronic" date-type="pub"><month>01</month><year>2022</year></pub-date>
<volume>3</volume>
<issue>1</issue>
<fpage>87</fpage>
<lpage>103</lpage>
<permissions><license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by-nc-sa/4.0/?utm"><license-p>CC BY-NC-SA 4.0</license-p></license></permissions>
<self-uri xlink:href="https://www.allmedicaljournal.com/article/548/development-of-the-oncosignal-algorithm-for-detecting-low-abundance-circulating-tumor-dna-signals"/>
<self-uri content-type="pdf" xlink:href="https://www.allmedicaljournal.com/article/548/download"/>
<abstract><p>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.</p></abstract>
<kwd-group kwd-group-type="author"><kwd>OncoSignal Algorithm</kwd><kwd>Circulating Tumor DNA</kwd><kwd>Low-Abundance ctDNA</kwd><kwd>Fragmentomics</kwd><kwd>Bayesian Evidence Fusion</kwd><kwd>Machine Learning</kwd></kwd-group>
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