Structural Inductive Biases in Emergent Communication

In order to communicate, humans flatten a complex representation of ideas and their attributes into a single word or a sentence. We investigate the impact of representation learning in artificial agents by developing graph referential games. We empirically show that agents parametrized by graph neural networks develop a more compositional language compared to bag-of-words and sequence models, which allows them to systematically generalize to new combinations of familiar features.Comment: The first two authors contributed equally. Poster presented at CogSci 202

Co-complex protein membership evaluation using Maximum Entropy on GO ontology and InterPro annotation.

MOTIVATION: Protein-protein interactions (PPI) play a crucial role in our understanding of protein function and biological processes. The standardization and recording of experimental findings is increasingly stored in ontologies, with the Gene Ontology (GO) being one of the most successful projects. Several PPI evaluation algorithms have been based on the application of probabilistic frameworks or machine learning algorithms to GO properties. Here, we introduce a new training set design and machine learning based approach that combines dependent heterogeneous protein annotations from the entire ontology to evaluate putative co-complex protein interactions determined by empirical studies. RESULTS: PPI annotations are built combinatorically using corresponding GO terms and InterPro annotation. We use a S.cerevisiae high-confidence complex dataset as a positive training set. A series of classifiers based on Maximum Entropy and support vector machines (SVMs), each with a composite counterpart algorithm, are trained on a series of training sets. These achieve a high performance area under the ROC curve of ≤0.97, outperforming go2ppi-a previously established prediction tool for protein-protein interactions (PPI) based on Gene Ontology (GO) annotations. AVAILABILITY AND IMPLEMENTATION: https://github.com/ima23/maxent-ppi. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Self-care Barriers Reported by Emergency Department Patients With Acute Heart Failure: A Sociotechnical Systems-based Approach

Study objective We pilot tested a sociotechnical systems-based instrument that assesses the prevalence and nature of self-care barriers among patients presenting to the emergency department (ED) with acute heart failure. Methods A semistructured instrument for measuring self-reported self-care barriers was developed and administered by ED clinicians and nonclinician researchers to 31 ED patients receiving a diagnosis of acute heart failure. Responses were analyzed with descriptive statistics and qualitative content analysis. Feasibility was assessed by examining participant cooperation rates, instrument completion times, item nonresponse, and data yield. Results Of 47 distinct self-care barriers assessed, a median of 15 per patient were indicated as “sometimes” or “often” present. Thirty-four specific barriers were reported by more than 25% of patients and 9 were reported by more than 50%. The sources of barriers included the person, self-care tasks, tools and technologies, and organizational, social, and physical contexts. Seven of the top 10 most prevalent barriers were related to patient characteristics; the next 3, to the organizational context (eg, life disruptions). A preliminary feasibility assessment found few item nonresponses or comprehension difficulties, good cooperation, and high data yield from both closed- and open-ended items, but also found opportunities to reduce median administration time and variability. Conclusion An instrument assessing self-care barriers from multiple system sources can be feasibly implemented in the ED. Further research is required to modify the instrument for widespread use and evaluate its implementation across institutions and cultural contexts. Self-care barriers measurement can be one component of broader inquiry into the distributed health-related “work” activity of patients, caregivers, and clinicians

Learning from Heterogeneous Data Sources: An Application in Spatial Proteomics.

Sub-cellular localisation of proteins is an essential post-translational regulatory mechanism that can be assayed using high-throughput mass spectrometry (MS). These MS-based spatial proteomics experiments enable us to pinpoint the sub-cellular distribution of thousands of proteins in a specific system under controlled conditions. Recent advances in high-throughput MS methods have yielded a plethora of experimental spatial proteomics data for the cell biology community. Yet, there are many third-party data sources, such as immunofluorescence microscopy or protein annotations and sequences, which represent a rich and vast source of complementary information. We present a unique transfer learning classification framework that utilises a nearest-neighbour or support vector machine system, to integrate heterogeneous data sources to considerably improve on the quantity and quality of sub-cellular protein assignment. We demonstrate the utility of our algorithms through evaluation of five experimental datasets, from four different species in conjunction with four different auxiliary data sources to classify proteins to tens of sub-cellular compartments with high generalisation accuracy. We further apply the method to an experiment on pluripotent mouse embryonic stem cells to classify a set of previously unknown proteins, and validate our findings against a recent high resolution map of the mouse stem cell proteome. The methodology is distributed as part of the open-source Bioconductor pRoloc suite for spatial proteomics data analysis.LMB was supported by a BBSRC Tools and Resources Development Fund (Award BB/K00137X/1) and a Wellcome Trust Technology Development Grant (108441/Z/15/Z). LG was supported by the European Union 7th Framework Program (PRIME-XS project, grant agreement number 262067) and a BBSRC Strategic Longer and Larger Award (Award BB/L002817/1). DW and OK acknowledge funding from the European Union (PRIME-XS, GA 262067) and Deutsche Forschungsgemeinschaft (KO-2313/6-1).This is the final version of the article. It first appeared from PLOS via https://doi.org/10.1371/journal.pcbi.100492

The Potential and Challenges of Nanopore Sequencing

A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of ‘third generation’ instruments that will sequence a diploid mammalian genome for ~$1,000 in ~24 h.Molecular and Cellular BiologyPhysic

Characterizing Emerging Canine H3 Influenza Viruses.

The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Nonstandard Errors

In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants