Abstract: The present disclosure provides systems and methods for machine learning classification and assessment of disease based on gene expression data. In an aspect, a method for determining a disease state of a subject may comprise: (a) assaying a biological sample obtained or derived from the subject to produce a data set comprising gene expression measurements of the biological sample at each of a plurality of disease-associated genomic loci; (b) computer processing the data set to determine the disease state of the subject; and (c) electronically outputting a report indicative of the disease state of the subject. In some embodiments, the plurality of disease-associated genomic loci comprises single nucleotide polymorphisms (SNPs). In some embodiments, the disease comprises a lupus condition. In some embodiments, the disease comprises cardiovascular disease (CVD).