Low-Bandwidth and Non-Compute Intensive Remote Identification of Microbes from Raw Sequencing Reads

Cheap high-throughput DNA sequencing may soon become routine not only for human genomes but also for practically anything requiring the identification of living organisms from their DNA: tracking of infectious agents, control of food products, bioreactors, or environmental samples. We propose a novel general approach to the analysis of sequencing data in which the reference genome does not have to be specified. Using a distributed architecture we are able to query a remote server for hints about what the reference might be, transferring a relatively small amount of data, and the hints can be used for more computationally-demanding work. Our system consists of a server with known reference DNA indexed, and a client with raw sequencing reads. The client sends a sample of unidentified reads, and in return receives a list of matching references known to the server. Sequences for the references can be retrieved and used for exhaustive computation on the reads, such as alignment. To demonstrate this approach we have implemented a web server, indexing tens of thousands of publicly available genomes and genomic regions from various organisms and returning lists of matching hits from query sequencing reads. We have also implemented two clients, one of them running in a web browser, in order to demonstrate that gigabytes of raw sequencing reads of unknown origin could be identified without the need to transfer a very large volume of data, and on modestly powered computing devices. A web access is available at http://tapir.cbs.dtu.dk. The source code for a python command-line client, a server, and supplementary data is available at http://bit.ly/1aURxkc

alan-turing-institute/MLJ.jl: v0.19.4

MLJ v0.19.4 <p><a href="https://github.com/alan-turing-institute/MLJ.jl/compare/v0.19.3...v0.19.4">Diff since v0.19.3</a></p> <p><strong>Merged pull requests:</strong></p> <ul> <li>Updating MLJBase.jl dep to last version (#1037) (@pebeto)</li> </ul&gt

alan-turing-institute/MLJ.jl: v0.20.0

MLJ v0.20.0 Diff since v0.19.5 (breaking) Adapt to the migration of measures from MLJBase.jl to StatisticalMeasures.jl (#1054). See the MLJBase 1.0 migration guide for details. Merged pull requests: CI: fix the YAML syntax for the docs job, and thus properly surface any docbuild failures (#1046) (@DilumAluthge) Update docs (#1048) (@ablaom) Try again to generate the documentation (#1049) (@ablaom) docs/make.jl: set devbranch to master, which means that the docs will be deployed for pushes to `master (#1051) (@DilumAluthge) Try to deploy docs again x 3 (#1052) (@ablaom) Adapt to migration of measures MLJBase.jl -> StatisticalMeasures.jl (#1054) (@ablaom) For a 0.20 release (#1060) (@ablaom) Closed issues: Julia crashes when fitting a SVC (#1030) Update deprecated document example in "Transformers ..." section of manual (#1040) fit! not exported in 0.19.3/0.19.4? (#1041) Doc generation is failing silently (#1045

alan-turing-institute/MLJ.jl: v0.20.1

MLJ v0.20.1 Diff since v0.20.0 (new feature) Add the BalancedModel wrapper from MLJBalancing.jl (#1064) (docs) Add the over/undersampling models from Imbalance.jl to the Model Browser (#1064) Merged pull requests: Add MLJBalancing to MLJ and add class imbalance docs (#1064) (@ablaom) For a 0.20.1 release (#1065) (@ablaom) Closed issues: Oversampling and undersampling (#661) [Tracking] Migration of measures MLJBase.jl -> StatisticalMeasures.jl (#1053) Include MLJBalancing.jl in MLJ and re-export it's names. (#1062) Update docs for new class imbalance support (#1063

alan-turing-institute/MLJ.jl: v0.19.5

MLJ v0.19.5 <p><a href="https://github.com/alan-turing-institute/MLJ.jl/compare/v0.19.4...v0.19.5">Diff since v0.19.4</a></p> <ul> <li>Correct problem with previous version in which some methods were not exported, namely: <code>source</code>, <code>node</code>, <code>fit!</code>, <code>freeze!</code>, <code>thaw!</code>, <code>Node</code>, <code>sources</code>, <code>origins</code> (#1043) @pebeto</li> </ul> <p><strong>Closed issues:</strong></p> <ul> <li>Is the Averager documentation deprecated? (#1039)</li> </ul> <p><strong>Merged pull requests:</strong></p> <ul> <li>Adding necessary exports (#1043) (@pebeto)</li> <li>For a 0.19.5 release (#1044) (@ablaom)</li> </ul&gt

alan-turing-institute/MLJ.jl: v0.19.3

MLJ v0.19.3 <p><a href="https://github.com/alan-turing-institute/MLJ.jl/compare/v0.19.2...v0.19.3">Diff since v0.19.2</a></p> <p><strong>Closed issues:</strong></p> <ul> <li>SymbolicRegression.jl — registry update (#1032)</li> </ul> <p><strong>Merged pull requests:</strong></p> <ul> <li>feat: Update ROADMAP.md be more understandable (#1031) (@MelihDarcanxyz)</li> <li>add sirus.jl and symbolicregression.jl models to model browser (#1033) (@OkonSamuel)</li> <li>Add MLJFlow for integration with MLflow logging platform (#1034) (@ablaom)</li> </ul&gt

O-phospho-L-serine, multi-functional excipient for B domain deleted recombinant factor VIII

Factor VIII (FVIII) is an important cofactor in the blood coagulation cascade. A deficiency or dysfunction of FVIII causes hemophilia A, a life-threatening bleeding disorder. FVIII circulates in plasma as a heterodimer comprising 6 domains (heavy chain, A1-A2-B and light chain A3-C1-C2). Replacement therapy using FVIII is the leading therapy in the management of hemophilia A. However, ∼15% to 30% of patients develop inhibitory antibodies that neutralize the activity of the protein. Neutralizing antibodies to epitopes in the lipid binding region of FVIII are commonly identified in patients' plasma. In this report, we investigated the effect of O-phospho-L-serine (OPLS), which binds to the lipid bindinding region, on the immunogenicity of B domain deleted recombinant factor VIII (BDDrFVIII). Sandwich enzyme-linked immunosorbent assay (ELISA) studies showed that OPLS specifically bind to the lipid binding region, localized in the C2 domain of the coagulation factor. Size exclusion chromatography and fluorescence anisotropy studies showed that OPLS interfered with the aggregation of BDDrFVIII. Immunogenicity of free-vs BDDrFVIII-OPLS complex was evaluated in a murine model of hemophilia A. Animals administered subcutaneous (sc) injections of BDDrFVIII-OPLS had lower neutralizing titers compared with animals treated with BDDRFVIII alone. Based on these studies, we hypothesize that specific molecular interactions between OPLS and BDDrFVIII may improve the stability and reduce the immunogenicity of BDDrFVIII formulations