Fold Family-Regularized Bayesian Optimization for Directed Protein Evolution

Directed Evolution (DE) is a technique for protein engineering that involves iterative rounds of mutagenesis and screening to search for sequences that optimize a given property (ex. binding affinity to a specified target). Unfortunately, the underlying optimization problem is under-determined, and so mutations introduced to improve the specified property may come at the expense of unmeasured, but nevertheless important properties (ex. subcellular localization). We seek to address this issue by incorporating a fold-specific regularization factor into the optimization problem. The regularization factor biases the search towards designs that resemble sequences from the fold family to which the protein belongs. We applied our method to a large library of protein GB1 mutants with binding affinity measurements to IgG-Fc. Our results demonstrate that the regularized optimization problem produces more native-like GB1 sequences with only a minor decrease in binding affinity. Specifically, the log-odds of our designs under a generative model of the GB1 fold family are between 41-45% higher than those obtained without regularization, with only a 7% drop in binding affinity. Thus, our method is capable of making a trade-off between competing traits. Moreover, we demonstrate that our active-learning driven approach reduces the wet-lab burden to identify optimal GB1 designs by 67%, relative to recent results from the Arnold lab on the same data

Defining the qualitative elements of Aichi Biodiversity Target 11 with regard to the marine and coastal environment in order to strengthen global efforts for marine biodiversity conservation outlined in the United Nations Sustainable Development Goal 14

The Convention on Biological Diversity (CBD) Aichi Target 11 states that, “by 2020, at least 17 per cent of terrestrial and inland water, and 10 per cent of coastal and marine areas, especially areas of particular importance for biodiversity and ecosystem services, are conserved through effectively and equitably managed, ecologically representative and well-connected systems of protected areas and other effective area-based conservation measures, and integrated into the wider landscapes and seascapes”. There has been rapid progress to meet the quantitative goal (the 10% target). However, the qualitative aspects of Aichi target 11 are less well described. The United Nations Sustainable Development Goal (SDG) 14 to “conserve and sustainably use the oceans, seas and marine resources for sustainable development” reaffirms the quantitative element of Aichi target 11, and, through the described sub-targets, places further emphasis on the economic and social context of global development. The complexity of the language from Aichi target 11 is not mirrored in SDG 14, leading to a potential scenario where the knowledge and progress towards Aichi Target 11 will be diluted as the focus shifts to the SDGs. This paper presents current knowledge and implementation of the qualitative elements of Aichi Target 11 and highlights gaps in knowledge. We conclude that the progress made so far on describing and implementing the qualitative goals of Aichi Target 11 should be integrated into SDG 14 in order to strengthen global efforts for marine biodiversity conservation and support the broader vision for sustainable development that will “transform our world”

An evaluation framework to determine the impact of the Lyme Bay Fisheries and Conservation Reserve and the activities of the Lyme Bay Consultative Committee on ecosystem services and human wellbeing.

This research evaluates the social and economic impact of the management measures that form the Lyme Bay Reserve and the partnership activities of the Lyme Bay Consultative Committee (LBCC) on Lyme Bay resource users. For the purpose of this evaluation it is the combination of the 2008 Statutory Instrument (SI) closure and the more recently designated Site of Community Interest (SCI) that form the boundary of the Lyme Bay Fisheries and Conservation Reserve, termed as the Lyme Bay Reserve. Data is analysed between 2005 and 2015. The results show that the habitats and species of Lyme Bay interact to support the delivery of several ecosystem processes (e.g. primary and secondary production, formation of species habitat) and the realisation of ecosystem services (e.g. fish for food). Overall it is clear that the closure of the area to mobile fishing gear has benefitted static gear fishermen by separating spatial conflict between gear types. The closure has enabled reef habitats to recover which in turn has supported increased catches of some reef associated species e.g. scallops. Further management and support measures agreed through the LBCC have clearly been successful in improving the well-being for those fishermen directly involved in the project. This research represents collaboration between Plymouth University, Exeter University, The Blue Marine Foundation and CEFAS. Input into the evaluation was provided by the Devon and Severn Inshore Fisheries and Conservation Authority (IFCA), the Southern IFCA, local fishermen and fishery representatives

galign: A Tool for Rapid Genome Polymorphism Discovery

BACKGROUND: Highly parallel sequencing technologies have become important tools in the analysis of sequence polymorphisms on a genomic scale. However, the development of customized software to analyze data produced by these methods has lagged behind. METHODS/PRINCIPAL FINDINGS: Here I describe a tool, 'galign', designed to identify polymorphisms between sequence reads obtained using Illumina/Solexa technology and a reference genome. The 'galign' alignment tool does not use Smith-Waterman matrices for sequence comparisons. Instead, a simple algorithm comparing parsed sequence reads to parsed reference genome sequences is used. 'galign' output is geared towards immediate user application, displaying polymorphism locations, nucleotide changes, and relevant predicted amino-acid changes for ease of information processing. To do so, 'galign' requires several accessory files easily derived from an annotated reference genome. Direct sequencing as well as in silico studies demonstrate that 'galign' provides lesion predictions comparable in accuracy to available prediction programs, accompanied by greater processing speed and more user-friendly output. We demonstrate the use of 'galign' to identify mutations leading to phenotypic consequences in C. elegans. CONCLUSION/SIGNIFICANCE: Our studies suggest that 'galign' is a useful tool for polymorphism discovery, and is of immediate utility for sequence mining in C. elegans

Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat

Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count

A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type

Engaging international students in employability activities: an innovative approach

This project aimed to investigate whether it will be effective to adopt social media to disseminate training opportunities and engage international students to develop their employability while they study in the UK. More specifically, three research objectives were: to examine international students’ opinions on usage of social media to engage them in different employability opportunities; to assess the effectiveness of the social media; to make recommendations to relevant student services for better engagement of international students. Background/context to project: Graduate employability has been widely debated by policy-makers and academics (Pegg et al., 2012). However, Waters (2009) points out that little reference is made in current literature to the increasingly international dimensions of higher education. Huang et al.’s (2014) research into graduate employability and Chinese international students in the UK argues that the students were fully aware of a range of opportunities available to support the development of their employability but their engagement with those opportunities could be better. Many authors recognise the importance of social media in engaging students in learning but few consider graduate employability. Furthermore, anecdotal evidence gathered through our previous research and our roles in supporting international students indicate that social media might address the current gapPedRI

ShortRead: a bioconductor package for input, quality assessment and exploration of high-throughput sequence data

Summary: ShortRead is a package for input, quality assessment, manipulation and output of high-throughput sequencing data. ShortRead is provided in the R and Bioconductor environments, allowing ready access to additional facilities for advanced statistical analysis, data transformation, visualization and integration with diverse genomic resources