Thera-SAbDab: the Therapeutic Structural Antibody Database

Raybould, Matthew I. J.; Marks, Claire; Lewis, Alan P.; Shi, Jiye; Bujotzek, Alexander; Taddese, Bruck; Deane, Charlotte M.

doi:10.1093/nar/gkz827

Cited by 123 publications

(118 citation statements)

References 19 publications

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“… 45 The tool calculates these metrics from homology models built using ABodyBuilder 42 and compares them to a database of 277 CSTs. 61 According to the metric in question, values are flagged as “amber” (extreme) if they lie outside the upper or lower, or upper and lower, 5% of observed values among CSTs. An antibody is flagged as “red” if the value of a particular metric is outside of the observed range in CSTs.…”

Section: Methodsmentioning

confidence: 99%

A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies

Richardson

Galson

Kellam

et al. 2021

mAbs

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Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However, current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies that can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis.

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Section: Methodsmentioning

confidence: 99%

A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies

Richardson

Galson

Kellam

et al. 2021

mAbs

Self Cite

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“…Both Total Raw and Ab-identified columns report the redundant number of sequences so as to exemplify the volume of antibody depositions in patent sequences -we report the number of unique heavy (H) and light (L) chains in the parentheses in column "Ab-identified". IMGT 21 , Antibody Society (http://www.antibodysociety.org) and Thera-SAbDab 22,23 , resulting in 563 unique INNs. We grouped the targets by number of patent families and therapeutic antibodies they were associated with.…”

Section: Resultsmentioning

confidence: 99%

“…Therapeutic antibodies in clinical use together with their associated targets were compiled from the WHO lists of International Nonproprietary Names 19 (INNs, e.g. list 122 20 ) IMGT 21 , Antibody Society (http://www.antibodysociety.org) and Thera-SAbDab 22,23 , resulting in 563 unique INNs. We grouped the targets by number of patent families and therapeutic antibodies they were associated with.…”

Section: Resultsmentioning

confidence: 99%

Data mining patented antibody sequences

Krawczyk¹,

Buchanan

Marcatili

2020

Preprint

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Patent literature should be a reflection of thirty years of engineering efforts in developing monoclonal antibody therapeutics. Such information is potentially valuable for rational antibody design. Patents however are not designed to convey scientific knowledge, but rather legal protection. It is unclear whether antibody information from patent documents, such as antibody sequences could be useful for the therapeutic antibody sphere in conveying engineering know-how rather than act as legal reference only. To assess the utility of patent data for therapeutic antibody engineering, we quantified the amount of antibody sequences in patents destined for medicinal purposes and how well they reflect the primary sequences of therapeutic antibodies in clinical use. We identified 16,526 patent families from major jurisdictions (e.g. USPTO and WIPO) that contained antibody sequences. These families held 245,109 unique antibody chains (135,397 heavy chains and 109,712 light chains) that we compiled in our Patented Antibody Database (PAD, http://naturalantibody.com/pad). We find that antibodies make up a non-trivial proportion of all patent amino acid sequence depositions (e.g. 10.95% of USPTO Full Text database). Our analysis of the 16,526 families demonstrates that the volume of patent documents with antibody sequences is growing with the majority of documents classified as containing antibodies for medicinal purposes. We further studied the 245,109 antibody chains from patent literature to reveal that they very well reflect the primary sequences of antibody therapeutics in clinical use. This suggests that patent literature could serve as a reference of previous engineering efforts to improve rational antibody design.

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“…Comparison to Antibody Therapeutics. The set of 89 therapeutics with 100% sequence identical structures (as of November 2019) were retrieved from Thera-SAbDab (34). A single structure was chosen for each therapeutic for the RMSD analysis; if multiple structures were available, we selected unbound structures with the best resolution.…”

Section: Clonotypingmentioning

confidence: 99%

Evidence of Antibody Repertoire Functional Convergence through Public Baseline and Shared Response Structures

Raybould¹,

Marks²,

Kovaltsuk³

et al. 2020

Preprint

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The antibody repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger a successful immune response in most people. Sequence-based approaches have so far offered little evidence for this phenomenon. For example, a recent study estimated the number of shared ('public') antibody clonotypes in circulating baseline repertoires to be around 0.02% across ten unrelated individuals. However, to engage the same epitope, antibodies only require a similar binding site structure and the presence of key paratope interactions, which can occur even when their sequences are dissimilar. Here, we investigate functional convergence in human antibody repertoires by comparing the antibody structures they contain. We first structurally profile baseline antibody diversity (using snapshots from 41 unrelated individuals), predicting all modellable distinct structures within each repertoire. This analysis uncovers a high degree of structural commonality. For instance, around 3% of distinct structures are common to the ten most diverse individual samples ('Public Baseline' structures). Our approach is the first computational method to provide support for the long-assumed levels of baseline repertoire functional commonality. We then apply the same structural profiling approach to repertoire snapshots from three individuals before and after flu vaccination, detecting a convergent structural drift indicative of recognising similar epitopes ('Public Response' structures). Antibody Model Libraries (AMLs) derived from Public Baseline and Public Response structures represent a powerful geometric basis set of low-immunogenicity candidates exploitable for general or target-focused therapeutic antibody screening. antibody repertoire | structural profiling | public structures | antibody model libraries | antibody screening Correspondence: deane@stats.ox.ac.uk

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Thera-SAbDab: the Therapeutic Structural Antibody Database

Cited by 123 publications

References 19 publications

A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies

A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-pertussis toxoid antibodies

Data mining patented antibody sequences

Evidence of Antibody Repertoire Functional Convergence through Public Baseline and Shared Response Structures

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