SCALOP: sequence-based antibody canonical loop structure annotation

Abstract

Motivation Canonical forms of the antibody complementarity-determining regions (CDRs) were first described in 1987 and have been redefined on multiple occasions since. The canonical forms are often used to approximate the antibody binding site shape as they can be predicted from sequence. A rapid predictor would facilitate the annotation of CDR structures in the large amounts of repertoire data now becoming available from next generation sequencing experiments. Results SCALOP annotates CDR canonical forms for antibody sequences, supported by an auto-updating database to capture the latest cluster information. Its accuracy is comparable to that of a standard structural predictor but it is 800 times faster. The auto-updating nature of SCALOP ensures that it always attains the best possible coverage. Availability and implementation SCALOP is available as a web application and for download under a GPLv3 license at opig.stats.ox.ac.uk/webapps/scalop . Supplementary information Supplementary data are available at Bioinformatics online.

Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice

“…In SAAB+, SCALOP annotates CDR-H1 and CDR-H2 sequences with structural canonical classes 22 , and FREAD predicts whether CDR-H3s from the Ig-seq data share a similar structure to a crystallographically-solved CDR-H3 structure 24 . We annotate predicted by FREAD the CDR-H3 sequence with the PDB code of the crystallographically-solved CDR-H3 structure (template).…”

“…To annotate the human and mouse data with structural information, we developed a customized version of our SAAB pipeline 15 , SAAB+ that predicts the structural shape of the IMGT-defined CDRs. CDR-H1 and CDR-H2 adopt a limited number of structural configurations, known as canonical classes 16,20,21 , which can be predicted accurately and rapidly from sequence 22 . SAAB+ uses SCALOP 22 to annotate non-CDR-H3 loop canonical classes.…”

“…CDR-H1 and CDR-H2 adopt a limited number of structural configurations, known as canonical classes 16,20,21 , which can be predicted accurately and rapidly from sequence 22 . SAAB+ uses SCALOP 22 to annotate non-CDR-H3 loop canonical classes. Canonical class annotation should be highly accurate, with SCALOP predictions estimated to be within 1.5 Å of the true structure 90% of the time 22 .…”

“…SAAB+ uses SCALOP 22 to annotate non-CDR-H3 loop canonical classes. Canonical class annotation should be highly accurate, with SCALOP predictions estimated to be within 1.5 Å of the true structure 90% of the time 22 . The June 2019 SCALOP database was used in this study.…”

Maturation of the human B-cell receptor repertoire with age

“…Crystallographic studies have shown that antibody CDR-H1 and CDR-H2 loops can adopt a very limited number of structural conformations, known as canonical loop classes (37,38). These canonical classes are considered to be separate and distinct structures of the CDRs and can be rapidly and accurately annotated by SCALOP (23). The proportion of sequences in which either CDR-H1 and CDR-H2 had switched from the canonical class of their germline increased with age for most antigen-experienced subsets, similar to the increasing mutation number with age ( Figure 2C).…”