In our latest immunoinformatics review, OPIG has teamed up with experienced antibody consultant Dr. Anthony Rees to outline the evidence for BCR/antibody repertoire convergence on common epitopes post-pathogen exposure, and all the ways we can go about detecting it from repertoire gene sequencing data. We highlight the new advances in the repertoire functional analysis field, including the role for OPIG’s latest tools for structure-aware antibody analytics: Structural Annotation of AntiBody repertoires+ (SAAB+), Paratyping, Ab-Ligity, Repertoire Structural Profiling & Structural Profiling of Antibodies to Cluster by Epitope (‘SPACE’).
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Antibodies for gut or bad
Over the last two decades, there has been mounting evidence of the role of the gut microbiome (the collection of microorganisms in the GI tract) in metabolic disorder (Fan and Pedersen 2021) and more recently, in psychiatric illness (Morais, Schreiber, and Mazmanian 2021). The maintenance of the equilibrium of commensal bacteria and their proper compartmentalization and stratification in the gut is critical for health.
There are diverse factors regulating microbiota composition (microbiota homeostasis) (Macpherson and McCoy 2013). I am principally interested in the role of antibodies – the idea that antibodies participate in this process is controversial (Kubinak and Round 2016) because of the difficulty of controlling for the multiple confounding environmental variables that influence the microbiome, but there are theories as to how this happens. The process of the shaping of the microbiota by antibodies was dubbed “antibody-mediated immunoselection” (AMIS) by (Kubinak and Round 2016).
Continue reading2021 likely to be a bumper year for therapeutic antibodies entering clinical trials; massive increase in new targets
Earlier this month the World Health Organisation (WHO) released Proposed International Nonproprietary Name List 125 (PL125), comprising the therapeutics entering clinical trials during the first half of 2021. We have just added this data to our Therapeutic Structural Antibody Database (Thera-SAbDab), bringing the total number of therapeutic antibodies recognised by the WHO to 711.
This is up from 651 at the end of 2020, a year which saw 89 new therapeutic antibodies introduced to the clinic. This rise of 60 in just the first half of 2021 bodes well for a record-breaking year of therapeutics entering trials.
Continue readingISMB 2021: epitope prediction tools
I recently had the opportunity to present my work on antibody virtual screening at the 2021 ISMB/ECCB virtual conference. In this blogpost, I want to summarise two research projects presented in the 3DSIG immunoinformatics session (in which I also presented my work) highlighting two different avenues of approaching epitope prediction (and immunoinformatics questions in general): Structure-based (Epitope3D) and sequence-based (SeRenDIP-CE).
Continue readingA to Z of Alternative Antibody Formats: Next-Generation Therapeutics
Do you know your diabodies from your zybodies?
Antibodies are a highly important class of therapeutics used to treat a range of diseases. Given their success as therapeutics, a wide variety of alternative antibody formats have been developed – these are driving the next generation of antibody therapeutics.
To note, this is not an exhaustive list but rather intended to demonstrate the range of existing antibody formats.
Inspired by this article in The Guardian: “Rachel Roddy’s A-Z of pasta“
Many of these figures were adapted from Spiess et al., 2015. Additionally, some of these formats have multiple variations or further possible forms (e.g., trispecific antibodies) – in these cases, one example is given here.
A – Antibodies
Antibodies – a fitting place to start this post. Antibodies are proteins produced by our immune systems to detect and protect against foreign pathogens. The ability of antibodies to bind molecules strongly and specifically – properties essential to their role in our immune defence – also make them valuable candidates for therapeutics. Antibody therapies have been developed for the treatment of various diseases, including cancers and viruses, and form a market estimated at over $100 billion1.
Continue readingCan few-shot language models perform bioinformatics tasks?
In 2019, I tried my hand at using large language models, specifically GPT-2, for text generation. In that blogpost, I used Hansard files to fine-tune the public release of GPT-2 to generate speeches by several speakers in the House of Commons (link).
In 2020, OpenAI released GPT-3, their new and improved text generation model (paper), which uses a whopping 175 billion parameters (as opposed to its predecessor’s 1.5 billion) and not only proved to be capable of state of the art performance on common text prediction benchmarks, but also generated a considerable amount of interest in the news media:
Continue readingDo antibodies care about sex?
In a recent OPIG antibody meeting, the topic of immune system differences between men and women came up. I thought this was cool and something I hadn’t read about, so what a brilliant topic for a blog most. This post is a high-level overview – I’ve listed the papers I’ve used at the bottom of this post so please consult them for more details!
Differences between males and females can lead to pretty big disparities in disease prevalence and outcomes. For example, non-reproductive cancers occur predominantly in males, whilst the majority of autoimmune disease occurs in females. Many factors may be impacting this, including environmental, genetic and hormonal influences, and much more research is required to fully understand these processes. Here I focus on sex-based biology, rather than gender, though both can influence the immune response.
Continue readingAntibody Binding is Mediated by a Compact Vocabulary of Paratope-Epitope Interactions
While my own research focuses mainly on what happens in an antibody before it binds its antigen, I recently came across a paper by Akbar et al [1] that examines antibody-antigen interactions using an elegant approach to identify a set of structural motifs that antibodies use to interact with their epitopes. Since I am interested in emergent properties that arise when a sequence is mapped onto an antibody structure, this paper was very exciting. I will also shamelessly admit that I’m a sucker for a pretty figure and this paper has many! Regardless, on to the findings!
The Coronavirus Antibody Database: 10 months on, 10x the data!
Back in May 2020, we released the Coronavirus Antibody Database (‘CoV-AbDab’) to capture molecular information on existing coronavirus-binding antibodies, and to track what we anticipated would be a boon of data on antibodies able to bind SARS-CoV-2. At the time, we had found around 300 relevant antibody sequences and a handful of solved crystal structures, most of which were characterised shortly after the SARS-CoV epidemic of 2003. We had no idea just how many SARS-CoV-2 binding antibody sequences would come to be released into the public domain…
10 months later (2nd March 2021), we now have tracked 2,673 coronavirus-binding antibodies, ~95% with full Fv sequence information and ~5% with solved structures. These datapoints originate from 100s of independent studies reported in either the academic literature or patent filings.
BioDataScience101: a fantastic initiative to learn bioinformatics and data science
Last Wednesday, I was fortunate enough to be invited as a guest lecturer to the 3rd BioDataScience101 workshop, an initiative spearheaded by Paolo Marcatili, Professor of Bioinformatics at the Technical University of Denmark (DTU). This session, on amino acid sequence analysis applied to both proteomics and antibody drug discovery, was designed and organised by OPIG’s very own Tobias Olsen.
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