Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data. DOI Creative Commons

Paweł Dudzic,

Dawid Chomicz,

Weronika Bielska

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

Abstract Antibody next-generation sequencing (NGS) datasets have become crucial to develop computational models addressing this successful class of therapeutics. Although antibodies are composed both heavy and light chains, most NGS depositions provide them in unpaired form, reducing their utility. Here we introduce PairedAbNGS, a novel database with paired heavy/light antibody chains. To the best our knowledge, is largest resource for natural sequences 58 bioprojects over 14 million assembled productive sequences. We make accessible at http://naturalantibody.com/paired-ngs as valuable tool biological machine-learning applications. Using dataset, investigated chain variable (V) gene pairing preferences found significant biases beyond usage frequencies, possibly due receptor editing favoring less autoreactive combinations. Analyzing available structures from Protein Data Bank, studied conserved contact residues between particularly interactions CDR3 region one FWR2 opposite chain. Examination amino acid pairs key sites revealed deviations acids distributions compared random pairings, chain’s contacting chain, indicating specific might be proper pairing. This observation further reinforced by preferential IGHV-IGLJ IGLV-IGHJ preferences. hope that resources findings would contribute improving engineering drugs.

Язык: Английский

RIOT - Rapid Immunoglobulin Overview Tool - annotation of nucleotide and amino acid immunoglobulin sequences using an open germline database. DOI Creative Commons

Paweł Dudzic,

Bartosz Janusz,

Tadeusz Satława

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 12, 2024

Antibodies are a cornerstone of the immune system, playing pivotal role in identifying and neutralizing infections caused by bacteria, viruses, other pathogens. Understanding their structure, function, can provide insights into both body's natural defenses principles behind many therapeutic interventions, including vaccines antibody-based drugs. The analysis annotation antibody sequences, identification variable, diversity, joining, constant genes, as well delineation framework regions complementarity-determining regions, is essential for understanding structure function. Currently analyzing large volumes sequences routine discovery, requiring fast accurate tools. While there existing tools designed numbering they often have limitations such being restricted to either nucleotide or amino acid reliance on non-uniform germline databases, slow execution times. Here we present Rapid Immunoglobulin Overview Tool (RIOT), novel open-source solution that addresses these shortcomings. RIOT handles sequence processing, comes with free database, computationally efficient. We hope tool will facilitate rapid sequencing outputs benefit biology discovering therapeutics.

Язык: Английский

Процитировано

1

RIOT—Rapid Immunoglobulin Overview Tool—annotation of nucleotide and amino acid immunoglobulin sequences using an open germline database DOI Creative Commons

Paweł Dudzic,

Bartosz Janusz,

Tadeusz Satława

и другие.

Briefings in Bioinformatics, Год журнала: 2024, Номер 26(1)

Опубликована: Ноя. 22, 2024

Abstract Antibodies are a cornerstone of the immune system, playing pivotal role in identifying and neutralizing infections caused by bacteria, viruses, other pathogens. Understanding their structure, function, can provide insights into both body’s natural defenses principles behind many therapeutic interventions, including vaccines antibody-based drugs. The analysis annotation antibody sequences, identification variable, diversity, joining, constant genes, as well delineation framework regions complementarity-determining regions, is essential for understanding structure function. Currently analyzing large volumes sequences routine discovery, requiring fast accurate tools. While there existing tools designed numbering they often have limitations such being restricted to either nucleotide or amino acid sequences; slow execution times; reliance on germline databases that closed, frequently changed, sparse coverage some species. Here, we present Rapid Immunoglobulin Overview Tool (RIOT), novel open-source solution addresses these shortcomings. RIOT handles sequence processing, comes integrated with an Open Germline Receptor Database, computationally efficient. We hope tool will facilitate rapid sequencing outputs benefit biology discovering therapeutics.

Язык: Английский

Процитировано

0

Conserved heavy/light contacts and germline preferences revealed by a large-scale analysis of natively paired human antibody sequences and structural data. DOI Creative Commons

Paweł Dudzic,

Dawid Chomicz,

Weronika Bielska

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 22, 2024

Abstract Antibody next-generation sequencing (NGS) datasets have become crucial to develop computational models addressing this successful class of therapeutics. Although antibodies are composed both heavy and light chains, most NGS depositions provide them in unpaired form, reducing their utility. Here we introduce PairedAbNGS, a novel database with paired heavy/light antibody chains. To the best our knowledge, is largest resource for natural sequences 58 bioprojects over 14 million assembled productive sequences. We make accessible at http://naturalantibody.com/paired-ngs as valuable tool biological machine-learning applications. Using dataset, investigated chain variable (V) gene pairing preferences found significant biases beyond usage frequencies, possibly due receptor editing favoring less autoreactive combinations. Analyzing available structures from Protein Data Bank, studied conserved contact residues between particularly interactions CDR3 region one FWR2 opposite chain. Examination amino acid pairs key sites revealed deviations acids distributions compared random pairings, chain’s contacting chain, indicating specific might be proper pairing. This observation further reinforced by preferential IGHV-IGLJ IGLV-IGHJ preferences. hope that resources findings would contribute improving engineering drugs.

Язык: Английский

Процитировано

0