High resolution population maps for low income nations: combining land cover and census in East Africa

Background

Between 2005 and 2050, the human population is forecast to grow by 2.7 billion, with the vast majority of this growth occurring in low income countries. This growth is likely to have significant social, economic and environmental impacts, and make the achievement of international development goals more difficult. The measurement, monitoring and potential mitigation of these impacts require high resolution, contemporary data on human population distributions. In low income countries, however, where the changes will be concentrated, the least information on the distribution of population exists. In this paper we investigate whether satellite imagery in combination with land cover information and census data can be used to create inexpensive, high resolution and easily-updatable settlement and population distribution maps over large areas.

Methodology/Principal Findings

We examine various approaches for the production of maps of the East African region (Kenya, Uganda, Burundi, Rwanda and Tanzania) and where fine resolution census data exists, test the accuracies of map production approaches and existing population distribution products. The results show that combining high resolution census, settlement and land cover information is important in producing accurate population distribution maps.

Conclusions

We find that this semi-automated population distribution mapping at unprecedented spatial resolution produces more accurate results than existing products and can be undertaken for as little as $0.01 per km². The resulting population maps are a product of the Malaria Atlas Project (MAP: http://www.map.ox.ac.uk) and are freely available.     

VMD DisRg: New User-Friendly Implement for calculation distance and radius of gyration in VMD program

Molecular dynamic simulation is a practical and powerful technique for analysis of protein structure. Several programs have been developed to facilitate the mentioned investigation, under them the visual molecular dynamic or VMD is the most frequently used programs. One of the beneficial properties of the VMD is its ability to be extendable by designing new plug-in. We introduce here a new facility of the VMD for distance analysis and radius of gyration of biopolymers such as protein and DNA.

Availability

The database is available for free at http://trc.ajums.ac.ir/HomePage.aspx/?TabID/=12618/&Site/=trc.ajums.ac/&Lang/=fa-IR     

OrFin: A web tool for detection of putative orthologs

Identification of ortholog is one of the important tasks to understand a novel genome. It helps to assign functional annotations, from one organism to another organism. To identify the putative ortholog, Reciprocal Best BLAST hit (RBBH) method is known to be an efficient approach. OrFin makes use of the same approach to identify pair of orthologous proteins for a given set of sequences of two species. It is a user-friendly web tool which works with user defined parameters to search RBBHs. Results are produced in both html and text format.

Availability

This web tool is freely available at http://bifl.uohyd.ac.in/orfin     

Mutationmapper: A Tool to Aid the Mapping of Protein Mutation Data

There has been a rapid increase in the amount of mutational data due to, amongst other things, an increase in single nucleotide polymorphism (SNP) data and the use of site-directed mutagenesis as a tool to help dissect out functional properties of proteins. Many manually curated databases have been developed to index point mutations but they are not sustainable with the ever-increasing volume of scientific literature. There have been considerable efforts in the automatic extraction of mutation specific information from raw text involving use of various text-mining approaches. However, one of the key problems is to link these mutations with its associated protein and to present this data in such a way that researchers can immediately contextualize it within a structurally related family of proteins. To aid this process, we have developed an application called MutationMapper. Point mutations are extracted from abstracts and are validated against protein sequences in Uniprot as far as possible. Our methodology differs in a fundamental way from the usual text-mining approach. Rather than start with abstracts, we start with protein sequences, which facilitates greatly the process of validating a potential point mutation identified in an abstract. The results are displayed as mutations mapped on to the protein sequence or a multiple sequence alignment. The latter enables one to readily pick up mutations performed at equivalent positions in related proteins. We demonstrate the use of MutationMapper against several examples including a single sequence and multiple sequence alignments. The application is available as a web-service at http://mutationmapper.bioch.ox.ac.uk.     

Chaste: An Open Source C++ Library for Computational Physiology and Biology

Chaste — Cancer, Heart And Soft Tissue Environment — is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to ‘re-invent the wheel’ with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials.

This is a PLOS Computational Biology Software Article

     

Discovery of protein phosphorylation motifs through exploratory data analysis

Background

The need for efficient algorithms to uncover biologically relevant phosphorylation motifs has become very important with rapid expansion of the proteomic sequence database along with a plethora of new information on phosphorylation sites. Here we present a novel unsupervised method, called Motif Finder (in short, F-Motif) for identification of phosphorylation motifs. F-Motif uses clustering of sequence information represented by numerical features that exploit the statistical information hidden in some foreground data. Furthermore, these identified motifs are then filtered to find “actual” motifs with statistically significant motif scores.

Results and Discussion

We have applied F-Motif to several new and existing data sets and compared its performance with two well known state-of-the-art methods. In almost all cases F-Motif could identify all statistically significant motifs extracted by the state-of-the-art methods. More importantly, in addition to this, F-Motif uncovers several novel motifs. We have demonstrated using clues from the literature that most of these new motifs discovered by F-Motif are indeed novel. We have also found some interesting phenomena. For example, for CK2 kinase, the conserved sites appear only on the right side of S. However, for CDK kinase, the adjacent site on the right of S is conserved with residue P. In addition, three different encoding methods, including a novel position contrast matrix (PCM) and the simplest binary coding, are used and the ability of F-motif to discover motifs remains quite robust with respect to encoding schemes.

Conclusions

An iterative algorithm proposed here uses exploratory data analysis to discover motifs from phosphorylated data. The effectiveness of F-Motif has been demonstrated using several real data sets as well as using a synthetic data set. The method is quite general in nature and can be used to find other types of motifs also. We have also provided a server for F-Motif at http://f-motif.classcloud.org/, http://bio.classcloud.org/f-motif/ or http://ymu.classcloud.org/f-motif/.     

Building a Better Fragment Library for De Novo Protein Structure Prediction

Fragment-based approaches are the current standard for de novo protein structure prediction. These approaches rely on accurate and reliable fragment libraries to generate good structural models. In this work, we describe a novel method for structure fragment library generation and its application in fragment-based de novo protein structure prediction. The importance of correct testing procedures in assessing the quality of fragment libraries is demonstrated. In particular, the exclusion of homologs to the target from the libraries to correctly simulate a de novo protein structure prediction scenario, something which surprisingly is not always done. We demonstrate that fragments presenting different predominant predicted secondary structures should be treated differently during the fragment library generation step and that exhaustive and random search strategies should both be used. This information was used to develop a novel method, Flib. On a validation set of 41 structurally diverse proteins, Flib libraries presents both a higher precision and coverage than two of the state-of-the-art methods, NNMake and HHFrag. Flib also achieves better precision and coverage on the set of 275 protein domains used in the two previous experiments of the the Critical Assessment of Structure Prediction (CASP9 and CASP10). We compared Flib libraries against NNMake libraries in a structure prediction context. Of the 13 cases in which a correct answer was generated, Flib models were more accurate than NNMake models for 10. “Flib is available for download at: http://www.stats.ox.ac.uk/research/proteins/resources”.     

A randomised controlled trial of ion-exchange water softeners for the treatment of eczema in children

Background

Epidemiological studies and anecdotal reports suggest a possible link between household use of hard water and atopic eczema. We sought to test whether installation of an ion-exchange water softener in the home can improve eczema in children.

Methods and Findings

This was an observer-blind randomised trial involving 336 children (aged 6 months to 16 years) with moderate/severe atopic eczema. All lived in hard water areas (≥200 mg/l calcium carbonate). Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care, or usual eczema care alone. The primary outcome was change in eczema severity (Six Area Six Sign Atopic Dermatitis Score, SASSAD) at 12 weeks, measured by research nurses who were blinded to treatment allocation. Analysis was based on the intent-to-treat population. Eczema severity improved for both groups during the trial. The mean change in SASSAD at 12 weeks was −5.0 (20% improvement) for the water softener group and −5.7 (22% improvement) for the usual care group (mean difference 0.66, 95% confidence interval −1.37 to 2.69, p = 0.53). No between-group differences were noted in the use of topical corticosteroids or calcineurin inhibitors.

Conclusions

Water softeners provided no additional benefit to usual care in this study population. Small but statistically significant differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias, since participants were aware of their treatment allocation. A detailed report for this trial is also available at http://www.hta.ac.uk.

Trial registration

Current Controlled Trials ISRCTN71423189 Please see later in the article for the Editors'' Summary     

BioCluster:Tool for Identification and Clustering of Enterobacteriaceae Based on Biochemical Data

Presumptive identification of different Enterobacteriaceae species is routinely achieved based on biochemical properties. Traditional practice includes manual comparison of each biochemical property of the unknown sample with known reference samples and inference of its identity based on the maximum similarity pattern with the known samples. This process is laborintensive, time-consuming, error-prone, and subjective. Therefore, automation of sorting and similarity in calculation would be advantageous. Here we present a MATLAB-based graphical user interface(GUI) tool named Bio Cluster. This tool was designed for automated clustering and identification of Enterobacteriaceae based on biochemical test results. In this tool, we used two types of algorithms, i.e., traditional hierarchical clustering(HC) and the Improved Hierarchical Clustering(IHC), a modified algorithm that was developed specifically for the clustering and identification of Enterobacteriaceae species. IHC takes into account the variability in result of 1–47 biochemical tests within this Enterobacteriaceae family. This tool also provides different options to optimize the clustering in a user-friendly way. Using computer-generated synthetic data and some real data, we have demonstrated that Bio Cluster has high accuracy in clustering and identifying enterobacterial species based on biochemical test data. This tool can be freely downloaded at http://microbialgen.du.ac.bd/biocluster/.     

VSDK: Virtual screening of small molecules using AutoDock Vina on Windows platform

Screening of ligand molecules to target proteins using computer-aided docking is a critical step in rational drug discovery. Based on this circumstance, we attempted to develop a virtual screening application system, named VSDK Virtual Screening by Docking, which can function under the Windows platform. This is a user-friendly, flexible, and versatile tool which can be used by users who are familiar with Windows OS. The virtual screening performance was tested for an arbitrarily-selected receptor, FGFR tyrosine kinase (pdb code: 1agw), by using ligands downloaded from ZINC database with its grid size of x,y,z = 30,30,30 and run number of 10. It took 90 minutes for 100 molecules for this virtual screening. VSDK is freely available at the designated URL, and a simplified manual can be downloaded from VSDK home page. This tool will have a more challenging scope and achievement as the computer speed and accuracy are increased and secured in the future.

Availability

The database is available for free at http://www.pharm.kobegakuin.ac.jp/˜akaho/english_top.html     

Complete genome sequence of the motile actinomycete Actinoplanes missouriensis 431T (= NBRC 102363T)

Actinoplanes missouriensis Couch 1963 is a well-characterized member of the genus Actinoplanes, which is of morphological interest because its members typically produce sporangia containing motile spores. The sporangiospores are motile by means of flagella and exhibit chemotactic properties. It is of further interest that members of Actinoplanes are prolific sources of novel antibiotics, enzymes, and other bioactive compounds. Here, we describe the features of A. missouriensis 431^T, together with the complete genome sequence and annotation. The 8,773,466 bp genome contains 8,125 protein-coding and 79 RNA genes.     

sTarPicker: a method for efficient prediction of bacterial sRNA targets based on a two-step model for hybridization

Background

Bacterial sRNAs are a class of small regulatory RNAs involved in regulation of expression of a variety of genes. Most sRNAs act in trans via base-pairing with target mRNAs, leading to repression or activation of translation or mRNA degradation. To date, more than 1,000 sRNAs have been identified. However, direct targets have been identified for only approximately 50 of these sRNAs. Computational predictions can provide candidates for target validation, thereby increasing the speed of sRNA target identification. Although several methods have been developed, target prediction for bacterial sRNAs remains challenging.

Results

Here, we propose a novel method for sRNA target prediction, termed sTarPicker, which was based on a two-step model for hybridization between an sRNA and an mRNA target. This method first selects stable duplexes after screening all possible duplexes between the sRNA and the potential mRNA target. Next, hybridization between the sRNA and the target is extended to span the entire binding site. Finally, quantitative predictions are produced with an ensemble classifier generated using machine-learning methods. In calculations to determine the hybridization energies of seed regions and binding regions, both thermodynamic stability and site accessibility of the sRNAs and targets were considered. Comparisons with the existing methods showed that sTarPicker performed best in both performance of target prediction and accuracy of the predicted binding sites.

Conclusions

sTarPicker can predict bacterial sRNA targets with higher efficiency and determine the exact locations of the interactions with a higher accuracy than competing programs. sTarPicker is available at http://ccb.bmi.ac.cn/starpicker/.     

Safety of postoperative administration of human urinary trypsin inhibitor in lung cancer patients with idiopathic pulmonary fibrosis

Background

Patients with idiopathic pulmonary fibrosis (IPF) undergoing pulmonary resection for lung cancer carry risks of acute exacerbations of IPF (AE) postoperatively. Currently, agents which may attenuate AE are actively sought. Urinary trypsin inhibitor, ulinastatin, is a synthetic glycoprotein which may potentially inhibit various inflammatory factors associated with the development and progression of IPF. The present study was done to evaluate the effects of administration of high dose ulinastatin in lung cancer patients with IPF immediately following lung resection.

Methods

Patients with IPFs radiologically diagnosed on high resolution CT, and histologically diagnosed resectable lung cancers, were eligible for the study. The effects of escalating doses of ulinastatin 3×10⁵, 6×10⁵, and 9×10⁵ units/body/day, administered postoperatively for 3 days were evaluated. The endpoints were safety and feasibility.

Results

Nine patients were evaluated, in cohorts of 3 patients per dosage. Postoperative follow up ranged from 3 to 12 months (median 9 months). The postoperative courses were uneventful in all patients. No subjective adverse events such as abdominal symptoms or skin rashes, or objective adverse events as per serum laboratory tests, such as liver or kidney dysfunctions potentially attributable to ulinastatin administration were observed. AE was seen in one patient at 3 months after surgery, but since this occurred shortly after administration of chemotherapy, it was considered to be attributable to the chemotherapy rather than surgery.

Discussion

Ulinastatin administration after lung resection in lung cancer patients with IPF was considered to be safe and feasible. Further study is planned at the highest dose of this study to evaluate efficacy.

Trial Registration

UMIN.ac.jp/ctr/UMIN000002410