What are the best resources for finding antibody sequences? Is there any trusted database for this? where you people look for finding out the sequences you want to work on.
IMGT ( http://www.imgt.org ) is the most comprehensive free database.
ABCD ( https://web.expasy.org/abcd/ ) is a manually curated depository of sequenced antibodies, at SIB Swiss Institute of Bioinformatics.
TABS is a good database for therapeutic antibodies ( https://tabs.craic.com/users/sign_in , however, it is not free)
SAbPred ( http://opig.stats.ox.ac.uk/webapps/newsabdab/sabpred/ ) SAbPred is a collection of computational tools (e.g., modeling software, developability prediction software) that make predictions about the properties of antibodies, focusing on their structures. Antibody informatics tools can help improve our understanding of immune responses to disease and aid in the design and engineering of therapeutic molecules.
SAbDab ( opig.stats.ox.ac.uk/webapps/newsabdab/sabdab/ ) contains all the antibody structures available in the PDB, annotated and presented in a consistent fashion. Each structure is annotated with a number of properties, including experimental details, antibody nomenclature (e.g., heavy-light pairings), curated affinity data and sequence annotations.
TheraSAbDab ( http://opig.stats.ox.ac.uk/webapps/newsabdab/therasabdab/search/ ) is a self-updating database of immunotherapeutic variable domain sequences and their corresponding structural representatives in SAbDab (which harvests data from the PDB). It updates alongside SAbDab on a weekly basis. It detects not only exact sequence matches to known structures, but also close sequence matches (divided into two categories: 95-98% seqID, or 99% seqID).
IMGT and structural therapeutic Ab databases I have been using. Thank you Annemarie Honegger for suggesting the other ones. Sometimes there is variation in sequences from these databases. Which one to trust in such cases.
Depends - some therapeutic antibodies have been engineered in multiple steps to reach the best final sequence for a particular application, e.g 4D5/Herceptin/Trastuzumab, where you can follow the original sequence/structure from the murine monoclonal over several stages of humanisation to the incorporation of addition functionality (meditope enabled variants). If it is critical, look at the associated publications
Also about the signal sequences, we do use same signal sequences for different mAbs. How to finalize the signal seq for different mAbs or one need to hit and trial with different signal seq.
For recombinant antibody production, you usually do not use the native antibody signal sequence (encoded by the V-gene), but a generic signal sequence that is optimal for the expression host you are using. Especially if you are expressing different antibodies, you usually prepare or get a vector that contains all but the variable domain sequences, while for the constant domains you use the isotype sequence that is best for your intended application, e.g. human IgG, and only insert the VH and VL sequences of the specific antibody. Depending on the expression host you are using, you may want to optimise the V-sequence codon usage.
The TABS database has the advantage that it also contains the sequences harvested from patents, which are normally not represented in the other databases unless they have also been published in the scientific literature. However, you have to mail to the curator of the database to learn whether you qualify for free academic access to the database.
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