Enabling comparative modeling of closely related genomes: Example genus Brucella

For many scientific applications, it is highly desirable to be able to compare metabolic models of closely related genomes. In this short report, we attempt to raise awareness to the fact that taking annotated genomes from public repositories and using them for metabolic model reconstructions is far from being trivial due to annotation inconsistencies. We are proposing a protocol for comparative analysis of metabolic models on closely related genomes, using fifteen strains of genus Brucella, which contains pathogens of both humans and livestock. This study lead to the identification and subsequent correction of inconsistent annotations in the SEED database, as well as the identification of 31 biochemical reactions that are common to Brucella, which are not originally identified by automated metabolic reconstructions. We are currently implementing this protocol for improving automated annotations within the SEED database and these improvements have been propagated into PATRIC, Model-SEED, KBase and RAST. This method is an enabling step for the future creation of consistent annotation systems and high-quality model reconstructions that will support in predicting accurate phenotypes such as pathogenicity, media requirements or type of respiration.We thank Jean Jacques Letesson, Maite Iriarte, Stephan Kohler and David O'Callaghan for their input on improving specific annotations. This project has been funded by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN272200900040C, awarded to BW Sobral, and from the United States National Science Foundation under Grant MCB-1153357, awarded to CS Henry. J.P.F. acknowledges funding from [FRH/BD/70824/2010] of the FCT (Portuguese Foundation for Science and Technology) Ph.D. scholarship

Utopia documents: linking scholarly literature with research data

Motivation: In recent years, the gulf between the mass of accumulating-research data and the massive literature describing and analyzing those data has widened. The need for intelligent tools to bridge this gap, to rescue the knowledge being systematically isolated in literature and data silos, is now widely acknowledged

Phosphorylation of centromeric histone H3 variant regulates chromosome segregation in S. cerevisiae

The centromeric histone H3 variant (CenH3) is essential for chromosome segregation in eukaryotes. We have identified posttranslational modifications of S. cerevisiae CenH3, Cse4. Functional characterization of cse4 phosphorylation mutants showed growth and chromosome segregation defects when combined with kinetochore mutants okp1 and ame1. Using a phosphoserine-specific antibody we showed that the association of phosphorylated Cse4 with centromeres is increased in response to defective microtubule attachment or reduced cohesion. We determined that evolutionarily conserved Ipl1/Aurora B contributes to phosphorylation of Cse4, as levels of phosphorylated Cse4 were reduced at centromeres in ipl1 strains in vivo and in vitro assays showed phosphorylation of Cse4 by Ipl1. Consistent with these results we observed that a phosphomimetic cse4-4SD mutant suppressed the temperature sensitive growth of ipl1-2 and Ipl1 substrate mutants dam1 spc34 and ndc80 that are defective for chromosome biorientation. Furthermore, cell biology approaches using a GFP labeled chromosome showed that cse4-4SD suppressed chromosome segregation defects in dam1 spc34 strains. Based these results we propose that phosphorylation of Cse4 destabilizes defective kinetochores to promote biorientation and ensure faithful chromosome segregation. Taken together, our study provides a detailed analysis, in vivo and in vitro, of Cse4 phosphorylation and its role in promoting faithful chromosome segregation

The global impact of tobacco control policies on smokeless tobacco use: a systematic review

BACKGROUND: Smokeless tobacco, used by more than 300 million people globally, results in substantial morbidity and mortality. For smokeless tobacco control, many countries have adopted policies beyond the WHO Framework Convention on Tobacco Control, which has been instrumental in reducing smoking prevalence. The impact of these policies (within and outside the Framework Convention on Tobacco Control) on smokeless tobacco use remains unclear. We aimed to systematically review policies that are relevant to smokeless tobacco and its context and investigate their impact on smokeless tobacco use. METHODS: In this systematic review, we searched 11 electronic databases and grey literature between Jan 1, 2005, and Sept 20, 2021, in English and key south Asian languages, to summarise smokeless tobacco policies and their impact. Inclusion criteria were all types of studies on smokeless tobacco users that mentioned any smokeless tobacco relevant policies since 2005, except systematic reviews. Policies issued by organisations or private institutions were excluded as well as studies on e-cigarettes and Electronic Nicotine Delivery System except where harm reduction or switching were evaluated as a tobacco cessation strategy. Two reviewers independently screened articles, and data were extracted after standardisation. Quality of studies was appraised using the Effective Public Health Practice Project's Quality Assessment Tool. Outcomes for impact assessment included smokeless tobacco prevalence, uptake, cessation, and health effects. Due to substantial heterogeneity in the descriptions of policies and outcomes, data were descriptively and narratively synthesised. This systematic review was registered in PROSPERO (CRD42020191946). FINDINGS: 14 317 records were identified, of which 252 eligible studies were included as describing smokeless tobacco policies. 57 countries had policies targeting smokeless tobacco, of which 17 had policies outside the Framework Convention on Tobacco Control for smokeless tobacco (eg, spitting bans). 18 studies evaluated the impact, which were of variable quality (six strong, seven moderate, and five weak) and reported mainly on prevalence of smokeless tobacco use. The body of work evaluating policy initiatives based on the Framework Convention on Tobacco Control found that these initiatives were associated with reductions in smokeless tobacco prevalence of between 4·4% and 30·3% for taxation and 22·2% and 70·9% for multifaceted policies. Two studies evaluating the non-Framework policy of sales bans reported significant reductions in smokeless tobacco sale (6·4%) and use (combined sex 17·6%); one study, however, reported an increased trend in smokeless tobacco use in the youth after a total sales ban, likely due to cross-border smuggling. The one study reporting on cessation found a 13·3% increase in quit attempts in individuals exposed (47·5%) to Framework Convention on Tobacco Control policy: education, communication, training, and public awareness, compared with non-exposed (34·2%). INTERPRETATION: Many countries have implemented smokeless tobacco control policies, including those that extend beyond the Framework Convention on Tobacco Control. The available evidence suggests that taxation and multifaceted policy initiatives are associated with meaningful reductions in smokeless tobacco use. FUNDING: UK National Institute for Health Research

Amino acid classification based spectrum kernel fusion for protein subnuclear localization

<p>Abstract</p> <p>Background</p> <p>Prediction of protein localization in subnuclear organelles is more challenging than general protein subcelluar localization. There are only three computational models for protein subnuclear localization thus far, to the best of our knowledge. Two models were based on protein primary sequence only. The first model assumed homogeneous amino acid substitution pattern across all protein sequence residue sites and used BLOSUM62 to encode <it>k</it>-mer of protein sequence. Ensemble of SVM based on different <it>k</it>-mers drew the final conclusion, achieving 50% overall accuracy. The simplified assumption did not exploit protein sequence profile and ignored the fact of heterogeneous amino acid substitution patterns across sites. The second model derived the <it>PsePSSM </it>feature representation from protein sequence by simply averaging the profile PSSM and combined the <it>PseAA </it>feature representation to construct a kNN ensemble classifier <it>Nuc-PLoc</it>, achieving 67.4% overall accuracy. The two models based on protein primary sequence only both achieved relatively poor predictive performance. The third model required that GO annotations be available, thus restricting the model's applicability.</p> <p>Methods</p> <p>In this paper, we only use the amino acid information of protein sequence without any other information to design a widely-applicable model for protein subnuclear localization. We use <it>K</it>-spectrum kernel to exploit the contextual information around an amino acid and the conserved motif information. Besides expanding window size, we adopt various amino acid classification approaches to capture diverse aspects of amino acid physiochemical properties. Each amino acid classification generates a series of spectrum kernels based on different window size. Thus, (I) window expansion can capture more contextual information and cover size-varying motifs; (II) various amino acid classifications can exploit multi-aspect biological information from the protein sequence. Finally, we combine all the spectrum kernels by simple addition into one single kernel called <it>SpectrumKernel+ </it>for protein subnuclear localization.</p> <p>Results</p> <p>We conduct the performance evaluation experiments on two benchmark datasets: <it>Lei </it>and <it>Nuc-PLoc</it>. Experimental results show that <it>SpectrumKernel+ </it>achieves substantial performance improvement against the previous model <it>Nuc-PLoc</it>, with overall accuracy <it>83.47% </it>against <it>67.4%</it>; and <it>71.23% </it>against <it>50% </it>of <it>Lei SVM Ensemble</it>, against 66.50% of <it>Lei GO SVM Ensemble</it>.</p> <p>Conclusion</p> <p>The method <it>SpectrumKernel</it>+ can exploit rich amino acid information of protein sequence by embedding into implicit size-varying motifs the multi-aspect amino acid physiochemical properties captured by amino acid classification approaches. The kernels derived from diverse amino acid classification approaches and different sizes of <it>k</it>-mer are summed together for data integration. Experiments show that the method <it>SpectrumKernel</it>+ significantly outperforms the existing models for protein subnuclear localization.</p

RAPID: Resource of Asian Primary Immunodeficiency Diseases

Availability of a freely accessible, dynamic and integrated database for primary immunodeficiency diseases (PID) is important both for researchers as well as clinicians. To build a PID informational platform and also as a part of action to initiate a network of PID research in Asia, we have constructed a web-based compendium of molecular alterations in PID, named Resource of Asian Primary Immunodeficiency Diseases (RAPID), which is available as a worldwide web resource at http://rapid.rcai.riken.jp/. It hosts information on sequence variations and expression at the mRNA and protein levels of all genes reported to be involved in PID patients. The main objective of this database is to provide detailed information pertaining to genes and proteins involved in primary immunodeficiency diseases along with other relevant information about protein–protein interactions, mouse studies and microarray gene-expression profiles in various organs and cells of the immune system. RAPID also hosts a tool, mutation viewer, to predict deleterious and novel mutations and also to obtain mutation-based 3D structures for PID genes. Thus, information contained in this database should help physicians and other biomedical investigators to further investigate the role of these molecules in PID