cAb-Rep

Similar antibody search


We provide 3 modes for searching similar antibody:

    I. CDR3 mode:
        The CDR3 mode searches antibody sequences having similar CDR3 motif. In this mode, please select heavy or light chain genes, and input an antibody siganture.
        The Signature must be defined using python regular expression format. Here we provide some examples to quickly generate your signatures:
            a. Motif VXXK, a four residue motif, X represents any amino acid, the signature should be: V[A-Z]{2}K, while [A-Z] means any amino acid, {2} means 2 consecutive positions are [A-Z]
            b. To search a five residue motif: X-X-[AFILMYWV]-[EQ]-X, [A-Z] is used for no specificity at a position, [AFILMYWV] means this position could be any of A,F,I,L,M,Y,W,V. So the final input signature should be: [A-Z]{2}[AFILMYWV][EQ][A-Z]
        In this mode, you can specify a V and J gene, otherwise the scripts will search all VJ gene combinations.

    II. Position mode:
        Position mode searches for antibodies having signature motifs at positions of interests. We provide 3 position schemes, defualt is Kabat. Here, the signature input is slightly different from the CDR3 mode, for example:          an input including both position and amino acid type as sigantures should be : 22,A,25,[GKS],50,K,60,[EQ]

    III. Blast mode:
        Blast mode is to search the most similar sequeneces in our database. The input requires sequences in fasta format, such as:
            >SRR4431789_00000182
            CAAGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCGGGGTCCTCGGTGAAGGTCTCCTGCAGGTCCTCTGGAGGAACCTTCAACAGTTTTGCTATCAGCTGGGTGC
        You can search multiple sequences at the same time, but more than 1000 sequences are not allowed.

Rarity of SHM search


Gene-specific subsitution profiles determine amino acid substitution preferences at each human V gene position (Sheng et al Front. Immunol 2017). To search the frequency of a somatic hypermutation at a position or to predict whether a substitution in a sequence is rare in a gene-specific subsitution profile, a V gene should be assigned and the cutoff for rare mutations (default is 0.5%) should be given. We provide 2 search modes for SHM rarity estimation:

    I. Sequence mode:
        In this mode, please choose the type of the input sequence . The sequences must be in fasta format and with proper translation frame when giving nucleotide sequences.

    II. Position mode:
        In this mode, please input the position, default is 52A, and amino acid substitutions of interest. Please seperate amino acids by comma (for example: N,F,H,D) when you have multiple amino acids.

Citation


Gene-specific subsitution profile:
Zizhang Sheng, Chaim A. Schramm, Rui Kong, NISC Comparative Sequencing Program, James C. Mullikin, John R. Mascola, Peter D. Kwong, and Lawrence Shapiro. Gene-specific substitution profiles describe the types and frequencies of amino acid changes during antibody somatic hypermutation. Front. Immunol. 8:537. doi: 10.3389/mmu.2017.00537 (2017).

cAb-Rep database:
Yicheng Guo, Kevin Chen, Peter D. Kwong, Lawrence Shaprio, and Zizhang Sheng. cAb-Rep: a database of curated antibody repertoires for exploring B cell response and predicting antibody prevalence. Front. Immunol. doi: 10.3389/fimmu.2019.02365 (2019).