Using Domain Based Latent Personal Analysis of B Cell Clone Diversity Patterns to Identify Novel Relationships Between the B Cell Clone Populations in Different Tissues

Abstract

The B cell population is highly diverse and very skewed. It is divided into clones (B cells with a common mother cell). It is thought that each clone represents an initial B cell receptor specificity. A few clones are very abundant, comprised of hundreds or thousands of B cells while the majority have only a few cells per clone. We suggest a novel method - domain-based latent personal analysis (LPA), a method for spectral exploration of entities in a domain, which can be used to find the spectral spread of sub repertoires within a person. LPA defines a domain-based spectral signature for each sub repertoire. LPA signatures consist of the elements, in our case - the clones, that most differentiate the sub repertoire from the person’s abundance of clones. They include both positive elements, which describe overabundant clones, and negative elements that describe missing clones. The signatures can also be used to compare the sub repertoires they represent to each other. Applying LPA to compare the repertoires found in different tissues, we reiterated previous findings that showed that gut and blood tissues have separate repertoires. We further identify a third branch of clonal patterns typical of the lymphatic organs (Spleen, MLN, and bone marrow) separated from the other two categories. We developed a python version of LPA analysis that can easily be applied to compare clonal distributions - https://github.com/ScanLab-ossi/LPA. It could also be easily adapted to study other skewed sequence populations used in the analysis of B cell receptor populations, for instance, k-mers and V gene usage. These analysis types should allow for inter and intra-repertoire comparisons of diversity, which could revolutionize the way we understand repertoire changes and diversity.