Abstract:BackgroundRecent technological advances in immune repertoire sequencing have created tremendous potential for advancing our understanding of adaptive immune response dynamics in various states of health and disease. Immune repertoire sequencing produces large, highly complex data sets, however, which require specialized methods and software tools for their effective analysis and interpretation.ResultsVDJServer is a cloud-based analysis portal for immune repertoire sequence data that provide access to a suite o… Show more
“…The portal is accessible through a standard web browser via a user-friendly graphical user interface, which facilitates use by research groups that lack bioinformatics expertise. Moreover, VDJServer provides free access to High Performance Computing (HPC) at the Texas Advanced Computing Center (63).…”
With the advent of high-throughput sequencing of immunoglobulins (Ig-Seq), the understanding of antibody repertoires and its dynamics among individuals and populations has become and exiting area of research. There are an increasing number of computational tools that aid in every step of the immune repertoire characterization. However, since not all tools function identically, every pipeline has its unique rationale and capabilities, creating a rich blend of useful features that may appear intimidating for newcomer laboratories with the desire to plunge into immune repertoire analysis to expand and improve their research; hence, all pipeline strengths and differences may not seem evident. In this review we provide an organized list of the current set of computational tools, focusing on their most attractive features and differences in order to carry out the characterization of antibody repertoires so that the reader better decides a strategic approach for the experimental design, and computational analyses of immune repertoires.
“…The portal is accessible through a standard web browser via a user-friendly graphical user interface, which facilitates use by research groups that lack bioinformatics expertise. Moreover, VDJServer provides free access to High Performance Computing (HPC) at the Texas Advanced Computing Center (63).…”
With the advent of high-throughput sequencing of immunoglobulins (Ig-Seq), the understanding of antibody repertoires and its dynamics among individuals and populations has become and exiting area of research. There are an increasing number of computational tools that aid in every step of the immune repertoire characterization. However, since not all tools function identically, every pipeline has its unique rationale and capabilities, creating a rich blend of useful features that may appear intimidating for newcomer laboratories with the desire to plunge into immune repertoire analysis to expand and improve their research; hence, all pipeline strengths and differences may not seem evident. In this review we provide an organized list of the current set of computational tools, focusing on their most attractive features and differences in order to carry out the characterization of antibody repertoires so that the reader better decides a strategic approach for the experimental design, and computational analyses of immune repertoires.
“…The large numbers of antibody sequences now becoming available in the public domain raise the possibility of natural sequences being found that are identical to commercial sequences 5 . This is especially pertinent in the face of large-scale organized efforts to make naturally sourced antibody NGS data 8 and analytics 9,10 more accessible 11 . Specifically, we recently created the Observed Antibody Space (OAS) database that curates the NGS antibody data from public archives and makes them available for easy processing 12 .…”
Recently it has become possible to query the great diversity of natural antibody repertoires using Next Generation Sequencing (NGS). These methods are capable of producing millions of sequences in a single experiment. Here we compare Clinical Stage Therapeutic antibodies to the ~1b sequences from 60 independent sequencing studies in the Observed Antibody Space Database. Of the 242 post Phase I antibodies, we find 16 with sequence identity matches of 95% or better for both heavy and light chains. There are also 54 perfect matches to therapeutic CDR-H3 regions in the NGS outputs, suggesting a nontrivial amount of convergence between naturally observed sequences and those developed artificially. This has potential implications for both the discovery of antibody therapeutics and the legal protection of commercial antibodies.
“…Some of these issues are addressed by services that provide Ig-seq-specific data deposition and analysis pipelines such as the B-T.CR wiki (https://b-t.cr), Imm-Port (http://immport.org) (26,27), immunoSEQ Analyzer (http:// clients.adaptivebiotech.com/), iReceptor (http://ireceptor.irmacs. sfu.ca/) (28), or VDJServer (http://vdjserver.org) (29). The iReceptor and the VDJServer are the main resources that fall under the umbrella of the organized effort of the Adaptive Immune Receptor Repertoire Community to provide standardized deposition and analysis pipelines for the Ig-seq outputs (24).…”
Abs are immune system proteins that recognize noxious molecules for elimination. Their sequence diversity and binding versatility have made Abs the primary class of biopharmaceuticals. Recently, it has become possible to query their immense natural diversity using next-generation sequencing of Ig gene repertoires (Ig-seq). However, Ig-seq outputs are currently fragmented across repositories and tend to be presented as raw nucleotide reads, which means nontrivial effort is required to reuse the data for analysis. To address this issue, we have collected Ig-seq outputs from 55 studies, covering more than half a billion Ab sequences across diverse immune states, organisms (primarily human and mouse), and individuals. We have sorted, cleaned, annotated, translated, and numbered these sequences and make the data available via our Observed Antibody Space (OAS) resource at http://antibodymap.org The data within OAS will be regularly updated with newly released Ig-seq datasets. We believe OAS will facilitate data mining of immune repertoires for improved understanding of the immune system and development of better biotherapeutics.
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