Does lack of exposure to individual antidepressants at different points during pregnancy associate with reduced risk of adverse newborn outcomes?

Background: The objective of this study was to determine if the lack of exposure to individual antidepressants at certain times in pregnancy improved maternal and infant outcomes.

Methods: This was a retrospective cohort study of 2741 pregnant women prescribed antidepressant(s) before or during pregnancy. Data were obtained from electronic medical records.

Epitope profiling using computational structural modelling demonstrated on coronavirus-binding antibodies.

Identifying the epitope of an antibody is a key step in understanding its function and its potential as a therapeutic. Sequence-based clonal clustering can identify antibodies with similar epitope complementarity, however, antibodies from markedly different lineages but with similar structures can engage the same epitope. We describe a novel computational method for epitope profiling based on structural modelling and clustering.

Comparing newborn outcomes after prenatal exposure to individual antidepressants: A retrospective cohort study.

Objective: To compare associations between individual antidepressants and newborn outcomes.

Design: Retrospective cohort study.

Setting: Deliveries in a large, US medical system.

Humanization of antibodies using a machine learning approach on large-scale repertoire data.

Motivation: Monoclonal antibody (mAb) therapeutics are often produced from non-human sources (typically murine), and can therefore generate immunogenic responses in humans. Humanization procedures aim to produce antibody therapeutics that do not elicit an immune response and are safe for human use, without impacting efficacy. Humanization is normally carried out in a largely trial-and-error experimental process.

Public Baseline and shared response structures support the theory of antibody repertoire functional commonality.

The naïve antibody/B-cell receptor (BCR) repertoires of different individuals ought to exhibit significant functional commonality, given that most pathogens trigger an effective antibody response to immunodominant epitopes. Sequence-based repertoire analysis has so far offered little evidence for this phenomenon. For example, a recent study estimated the number of shared ('public') antibody clonotypes in circulating baseline repertoires to be around 0.

CoV-AbDab: the coronavirus antibody database.

Motivation: The emergence of a novel strain of betacoronavirus, SARS-CoV-2, has led to a pandemic that has been associated with over 700 000 deaths as of August 5, 2020. Research is ongoing around the world to create vaccines and therapies to minimize rates of disease spread and mortality. Crucial to these efforts are molecular characterizations of neutralizing antibodies to SARS-CoV-2.

How repertoire data are changing antibody science.

Antibodies are vital proteins of the immune system that recognize potentially harmful molecules and initiate their removal. Mammals can efficiently create vast numbers of antibodies with different sequences capable of binding to any antigen with high affinity and specificity. Because they can be developed to bind to many disease agents, antibodies can be used as therapeutics.

TCRBuilder: multi-state T-cell receptor structure prediction.

Motivation: T-cell receptors (TCRs) are immune proteins that primarily target peptide antigens presented by the major histocompatibility complex. They tend to have lower specificity and affinity than their antibody counterparts, and their binding sites have been shown to adopt multiple conformations, which is potentially an important factor for their polyspecificity. None of the current TCR-modelling tools predict this variability which limits our ability to accurately predict TCR binding.

Structural diversity of B-cell receptor repertoires along the B-cell differentiation axis in humans and mice.

Most current analysis tools for antibody next-generation sequencing data work with primary sequence descriptors, leaving accompanying structural information unharnessed. We have used novel rapid methods to structurally characterize the complementary-determining regions (CDRs) of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated CDRs provide unprecedented insights into both the structural predetermination and dynamics of the adaptive immune response.

Thera-SAbDab: the Therapeutic Structural Antibody Database.

The Therapeutic Structural Antibody Database (Thera-SAbDab; http://opig.stats.ox.

Five computational developability guidelines for therapeutic antibody profiling.

Therapeutic mAbs must not only bind to their target but must also be free from "developability issues" such as poor stability or high levels of aggregation. While small-molecule drug discovery benefits from Lipinski's rule of five to guide the selection of molecules with appropriate biophysical properties, there is currently no in silico analog for antibody design. Here, we model the variable domain structures of a large set of post-phase-I clinical-stage antibody therapeutics (CSTs) and calculate in silico metrics to estimate their typical properties.

Increasing the accuracy of protein loop structure prediction with evolutionary constraints.

Motivation: Accurate prediction of loop structures remains challenging. This is especially true for long loops where the large conformational space and limited coverage of experimentally determined structures often leads to low accuracy. Co-evolutionary contact predictors, which provide information about the proximity of pairs of residues, have been used to improve whole-protein models generated through de novo techniques.

Predicting loop conformational ensembles.

Motivation: Protein function is often facilitated by the existence of multiple stable conformations. Structure prediction algorithms need to be able to model these different conformations accurately and produce an ensemble of structures that represent a target's conformational diversity rather than just a single state. Here, we investigate whether current loop prediction algorithms are capable of this.

Sphinx: merging knowledge-based and ab initio approaches to improve protein loop prediction.

Motivation: Loops are often vital for protein function, however, their irregular structures make them difficult to model accurately. Current loop modelling algorithms can mostly be divided into two categories: knowledge-based, where databases of fragments are searched to find suitable conformations and ab initio, where conformations are generated computationally. Existing knowledge-based methods only use fragments that are the same length as the target, even though loops of slightly different lengths may adopt similar conformations.

SAbPred: a structure-based antibody prediction server.

SAbPred is a server that makes predictions of 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. SAbPred is a single platform containing multiple applications which can: number and align sequences; automatically generate antibody variable fragment homology models; annotate such models with estimated accuracy alongside sequence and structural properties including potential developability issues; predict paratope residues; and predict epitope patches on protein antigens.