Examining the sublineage structure of Mycobacterium tuberculosis complex strains with multiple-biomarker tensors

Cagri Ozcaglar, Amina Shabbeer, Scott L. Vandenberg, Bülent Yener, Kristin P. Bennett

Abstract: Strains of the Mycobacterium tuberculosis complex (MTBC) can be classified into coherent lineages of similar traits based on their genotype. We present a tensor clustering framework to group MTBC strains into sublineages of the known major lineages based on two biomarkers: spacer oligonucleotide type (spoligotype) and mycobacterial interspersed repetitive units (MIRU). We represent genotype information of MTBC strains in a high-dimensional array in order to include information about spoligotype, MIRU, and their coexistence using multiple-biomarker tensors. We use multiway models to transform this multidimensional data about the MTBC strains into two-dimensional arrays and use the resulting score vectors in a stable partitive clustering algorithm to classify MTBC strains into sublineages. We validate clusterings using cluster stability and accuracy measures, and find stabilities of each cluster. Based on validated clustering results, we present a sublineage structure of MTBC strains and compare it to the sublineage structures of SpolDB4 and MIRU-VNTRplus.