Enriching Ig-seq datasets with structural information should improve analyses and insights that can be derived from antibody repertoire snapshots.

Predicting the shape of a sequence can offer sufficient information to link it to an antibody with similar shape and defined antigen specificity ( 22, 23). ( 20), structural information can give both an overall predicted shape and detail of the binding site (CDRs). In this paper, we show it is possible to characterize structurally large percentages of the data and describe a pipeline for automating the task.Īs described by Kovaltsuk et al. 175,000 sequences) but they did not produce a structural annotation protocol ( 21). In one study, the authors structurally characterized a small portion of their Ig-seq data (ca. These studies do not consider the three-dimensional structure of the antibody, but it is this structure that dictates antigen recognition ( 19, 20). The outputs from these Ig-seq experiments have been characterized by their germline biases and sequence analysis methods ( 2, 10, 14, 17, 18). Next-generation sequencing of immunoglobulin genes (Ig-seq) facilitates this task as it allows us to obtain a snapshot of the B-cell receptor (antibody) repertoire across different individuals and immune states ( 11– 16). Such binding malleability of antibodies has long been a subject of intensive academic and industrial research.ĭiscerning human antibody diversity will help us to understand how our immune system is capable of recognizing such a myriad set of antigens and underpins our ability to exploit them therapeutically ( 7– 10). Thus, in a single individual, there is likely to exist an antibody capable of recognizing an arbitrary antigen, though perhaps not specifically. It is estimated that a typical human is capable of producing more than 10 10 distinct antibody molecules ( 2– 6). There is a limited set of known human germline framework sequences (~150), but CDRs, which dictate antigen recognition, show more variation ( 1). 110 amino acids long, composed of the framework region and three hypervariable loops referred to as complementarity determining regions (CDRs). Each of the chains has a variable region that is ca. In humans, they are composed of two polypeptide chains, referred to as heavy and light. They are produced by B-cells, where they can be secreted or act as a membrane-bound B-cell receptor. Antibodies are proteins that play a key role in recognizing potentially noxious molecules (antigens) in jawed vertebrates.

Size of antibody repertoire