Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB): characterizing clusters of differentiation within a compendium of systemic lupus erythematosus patients.

Clusters of differentiation (CD) are cell surface biomarkers that denote key biological differences between cell types and disease state. CD-targeting therapeutic monoclonal antibodies (mABs) afford rich trans-disease repositioning opportunities. Within a compendium of systemic lupus erythematous (SLE) patients, we applied the Integrated machine learning pipeline for aberrant biomarker enrichment (i-mAB) to profile de novo gene expression features affecting CD20, CD22 and CD30 gene aberrance. First, a novel Relief-based algorithm identified interdependent features(p=681) predicting treatment-naïve SLE patients (balanced accuracy=0.822). We then compiled CD-associated expression profiles using regularized logistic regression and pathway enrichment analyses. On an independent general cell line model system data, we replicated associations (in silico) of BCL7A (padj=1.69e-9) and STRBP(padj=4.63e-8) with CD22; NCOA2(padj=7.00e-4), ATN1 (padj=1.71e-2), and HOXC4(padj=3.34e-2) with CD30; and PHOSPHO1, a phosphatase linked to bone mineralization, with both CD22(padj=4.37e-2) and CD30(padj=7.40e-3). Utilizing carefully aggregated secondary data and leveraging a priori hypotheses, i-mAB fostered robust biomarker profiling among interdependent biological features.