Heterogeneous Sequences Research Articles

Power estimation for non-standardized multisite studies

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions.

Advanced treatment of oilfield production wastewater by an integration of coagulation/flotation, catalytic ozonation and biological processes

ABSTRACTIn this study, advanced treatment of heavily polluted oilfield production wastewater (OPW) was investigated employing the combination of coagulation/dissolved air flotation, heterogeneous catalytic ozonation and sequencing batch reactor (SBR) processes. Two SBR reactors were separately set up before and after the ozonation unit. The results show that microbubble flotation was more efficient than macrobubble flotation in pollutant removal. Catalytic ozonation with the prepared Fe/activated carbon catalyst significantly enhanced pollutant removal in the second SBR by improving wastewater biodegradability and reducing wastewater microtoxicity. The treatment technique decreased oil, chemical oxygen demand and NH3-N by about 97%, 88% and 91%, respectively, allowing the discharge limits to be met. Therefore, the integrated process with efficient, economical and sustainable advantages was suitable for advanced treatment of real OPW.

Shearing along faults and stratigraphic joints controlled by land subsidence in the Valley of Queretaro, Mexico

Slip of nearly vertical faults or horizontal stratigraphic joints has provoked the shearing of at least 16 well casings in a period of over 10 years in the Valley of Queretaro aquifer, Mexico. Evidence integrated from field observations, remote surface-deformation monitoring, in-situ monitoring, stratigraphic correlation, and numerical modeling indicate that groundwater depletion and land subsidence induce shearing. Two main factors conditioning the stress distribution and the location of sheared well casings have been identified: (1) slip on fault planes, and (2) slip on stratigraphic joints. Additionally, the distribution of piezometric gradients may be a factor that enhances shearing. Slip on faults can be generated either by the compaction of sedimentary units (passive faulting) or by slip of blocks delimited by pre-existing faults (reactivation). Major piezometric-level declines and the distribution of hydraulic gradients can also be associated with slip at stratigraphic joints. Faults and hydraulic contrasts in the heterogeneous rock sequence, along with groundwater extraction, influence the distribution of the gradients and delimit the compartments of groundwater in the aquifer. Analogue modeling allowed assessment of the distribution of stress–strain and displacements associated with the increase of the vertical stress. Fault-bounded aquifers in grabens are common in the central part of Mexico and the results obtained can be applied to other subsiding, structurally controlled aquifer systems elsewhere.

Infections Caused By Community-Associated Methicillin-Resistant Staphylococcus Aureus European Clone (ST80) In Slovenia Between 2006 And 2013: PRIKAZ PRIMEROV OKUŽB, POVZROČENIH S PROTI METICILINU ODPORNO BAKTERIJO STAPHYLOCOCCUS AUREUS, DOMAČEGA OKOLJA, KI PRIPADA EVROPSKEMU KLONU (ST80) V SLOVENIJI V OBDOBJU MED 2006 IN 2013.

IntroductionAccording to the existing literature, a heterogeneous sequence type (ST) or clones of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) circulate in Europe. In Europe, the European clone that belongs to sequence type ST80 is predominant.MethodsThe aim of the study was to investigate the phenotypic and genotypic characteristics and epidemiological data of CA-MRSA ST80 and its occurrence in Slovenia. We retrospectively analyzed those CA-MRSA isolates that were isolated during microbiological procedures in microbiological laboratories between 2006 and 2013. Only CA-MRSA isolates from the national collection of CA-MRSA strains that belonged to ST80 (European clone) were analyzed. We determined the Pantone-Valentine leukocidin (PVL), mec A genes, exfoliative toxin genes and type of staphylococcal cassette chromosome (SCCmec) by polymerase chain reaction (PCR). We determined also spa type and sequence type.ResultsST80 was confirmed in only 2 (0.5%) out of 385 CA-MRSA isolates, collected in a national collection of CAMRSA. Both isolates were positive for the PVL genes, mec A gene, exfoliative toxin type D gene and SCCmec IV. One CA-MRSA isolate was confirmed in a wound swab taken from a 47-year-old male, and the second was isolated from blood cultures of a 69-year-old female. No epidemiological connections between them were found.ConclusionsIn Slovenia CA-MRSA infections caused by ST80 are rare. In the future, it is necessary that a surveillance study of CA-MRSA at the national level continues and CA-MRSA be considered as a public health threat.

Multiple episodes of partial melting, depletion, metasomatism and enrichment processes recorded in the heterogeneous upper mantle sequence of the Neotethyan Eldivan ophiolite, Turkey

The Eldivan ophiolite along the Izmir–Ankara–Erzincan suture zone in north-central Anatolia represents a remnant of the Neotethyan oceanic lithosphere. Its upper mantle peridotites include three lithologically and compositionally distinct units: clinopyroxene (cpx)–harzburgite and lherzolite (Group-1), depleted harzburgite (Group-2), and dunite (Group-3). Relics of primary olivine and pyroxene occur in the less refractory harzburgites, and fresh chromian spinel (Cr-spinel) is ubiquitous in all peridotites. The Eldivan peridotites reflect a petrogenetic history evolving from relatively fertile (lherzolite and cpx–harzburgite) toward more depleted (dunite) compositions through time, as indicated by (i) a progressive decrease in the modal cpx distribution, (ii) a progressive increase in the Cr#s [Cr/(Cr+Al)] of Cr-spinel (0.15–0.78), and (iii) an increased depletion in the whole-rock abundances of some magmaphile major oxides (Al2O3, CaO, SiO2 and TiO2) and incompatible trace elements (Zn, Sc, V and Y). The primitive mantle-normalized REE patterns of the Group-1 and some of the Group-2 peridotites display LREE depletions. Higher YbN and lower SmN/YbN ratios of these rocks are compatible with their formation after relatively low degrees (9–25%) of open-system dynamic melting (OSDM) of a Depleted Mid-ocean ridge Mantle (DMM) source, which was then fluxed with small volumes of oceanic mantle-derived melt [fluxing ratio (β): 0.7–1.2%]. Accessory Cr-spinel compositions (Cr#=015–0.53) of these rocks are consistent with their origin as residual peridotites beneath a mid-ocean ridge axis. Part of the Group-2 harzburgites exhibit lower YbN and higher SmN/YbN ratios, LREE-enriched REE patterns, and higher Cr-spinel Cr#s ranging between 0.54 and 0.61. Trace element compositions of these peridotites can be modeled by approximately 15% OSDM of a previously 17% depleted DMM, which was then fluxed (β: 0.4%) with subduction-influenced melt. The Group-3 dunite samples contain Cr-spinel with elevated Cr#s (0.73–0.78) and low-TiO2 contents (<0.13wt.%), implying higher degrees of melting (21–24%) of an already depleted DMM that was triggered by infiltration of low-Ti boninite melt with fluxing rates of 0.4–4.0%. The existence of interstitial, idiomorphic Cr-spinel (high Cr# and low Ti) in the Group-3 dunites is consistent with this interpretation. The occurrence of both MOR- and SSZ-type peridotites in the Eldivan ophiolite suggests that its heterogeneous upper mantle was produced as a result of different partial melting and melt–rock reaction processes in different tectonic settings within the Neotethyan realm.

Van der Waals interactions between polymers with sequence-specific polarizabilities: Stiff polymers and Gaussian coils

We consider the van der Waals interaction between a pair of polymers with quenched heterogeneous sequences of local polarizabilities along their backbones, and study the effective pairwise interaction energy for both stiff polymers and flexible Gaussian coils. In particular, we focus on the cases where the pair of polarizability sequences are (i) distinct and (ii) identical. We find that the pairwise interaction energies of distinct and identical Gaussian coils are both isotropic and exhibit the same decay behavior for separations larger than their gyration radius, in contradistinction to the orientationally anisotropic interaction energies of distinct and identical stiff polymers. For both Gaussian coils and stiff polymers, the attractive interaction between identical polymers is enhanced if the polarizability sequence is more heterogeneous.

Sequence heterogeneity accelerates protein search for targets on DNA

The process of protein search for specific binding sites on DNA is fundamentally important since it marks the beginning of all major biological processes. We present a theoretical investigation that probes the role of DNA sequence symmetry, heterogeneity, and chemical composition in the protein search dynamics. Using a discrete-state stochastic approach with a first-passage events analysis, which takes into account the most relevant physical-chemical processes, a full analytical description of the search dynamics is obtained. It is found that, contrary to existing views, the protein search is generally faster on DNA with more heterogeneous sequences. In addition, the search dynamics might be affected by the chemical composition near the target site. The physical origins of these phenomena are discussed. Our results suggest that biological processes might be effectively regulated by modifying chemical composition, symmetry, and heterogeneity of a genome.

Shear-zone hosted copper mineralisation of the Omitiomire deposit — Structural controls of fluid flow and mineralisation during subduction accretion in the Pan-African Damara Belt of Namibia

The Omitiomire copper deposit is a relatively recent discovery in the Pan-African Damara Belt of central Namibia. The deposit is situated in Mesoproterozoic gneisses and amphibolites of the Ekuja Dome overlain by amphibolite-grade metaturbidites of the Southern Zone accretionary prism that formed during northward subduction of the Kalahari Craton below the Congo Craton between ca. 580–520Ma. Copper mineralisation is confined to an anastomosing system of shallowly-dipping, retrograde mylonitic shear zones within the Ekuja Dome. The shear zones are centred around a lithologically heterogeneous amphibolite-gneiss sequence. Mylonitisation and copper mineralisation are closely associated with the retrogression of particularly amphibolites and the partial or complete replacement of amphibolites by biotite–epidote and biotite–chlorite–epidote schists that host the chalcocite-dominated mineralisation.Deformation and mineralisation in the heterogeneous shear-zone system can be shown to describe a progression. Initial strain localization is confined to lithological (amphibolite-gneiss) contacts and associated quartz veining and fluid flow are preferentially developed around the margins of competent amphibolite units. Fluid infiltration and the retrogression of amphibolites to biotite–epidote schists leads to strain localization into the marginal schists that envelop amphibolites. Further veining and fluid flow are localised into the central parts of amphibolite units leading to the pervasive retrogression to biotite–epidote schists that dominate the central parts of the shear-zone system. Earlier quartz-vein generations appear as isoclinally folded and dismembered ribbons or boudins in mineralised schists. The clearly syntectonic introduction of the copper mineralisation is underlined by the intergrowth of chalcocite with the retrograde assemblages and chalcocite forming part of the mylonitic shear-zone fabric.3D modelling of drillhole data combined with limited surface exposure delineates a shallow east dipping, gently undulating ore body parallel to the regional gneissosity of the Ekuja Dome. The ore body comprises several mineralised lenses varying in thickness from 10m to >100m. Prominent ore shoots are gently doubly plunging to the N and S and parallel to the regionally developed L>S fabric in the gneisses. Kinematic indicators in the mineralised shear zone system point to a top-to-the S sense of shear, parallel to the regional L fabric and parallel to the southverging transport recorded in the structurally overlying prism metasediments.The regional setting of the Omitiomire deposit, kinematics, and retrograde, but high-temperature overprint of original mineral assemblages in the mineralised shear zones indicate deformation and fluid flow during the expulsion of the basement gneisses during N-ward direction subduction of the Kalahari Craton below the Congo Craton. Lithological, geochronological, structural and P–T data suggest numerous similarities and, indeed, correlations between the Omitiomire-style copper mineralisation of the Damara Belt with the large copper deposits hosted by basement gneisses in the Domes Region of the Lufilian Arc in Zambia.

MixChIP: a probabilistic method for cell type specific protein-DNA binding analysis.

BackgroundTranscription factors (TFs) are proteins that bind to DNA and regulate gene expression. To understand details of gene regulation, characterizing TF binding sites in different cell types, diseases and among individuals is essential. However, sometimes TF binding can only be measured from biological samples that contain multiple cell or tissue types. Sample heterogeneity can have a considerable effect on TF binding site detection. While manual separation techniques can be used to isolate a cell type of interest from heterogeneous samples, such techniques are challenging and can change intra-cellular interactions, including protein-DNA binding. Computational deconvolution methods have emerged as an alternative strategy to study heterogeneous samples and numerous methods have been proposed to analyze gene expression. However, no computational method exists to deconvolve cell type specific TF binding from heterogeneous samples.ResultsWe present a probabilistic method, MixChIP, to identify cell type specific TF binding sites from heterogeneous chromatin immunoprecipitation sequencing (ChIP-seq) data. Our method simultaneously estimates the binding strength in different cell types as well as the proportions of different cell types in each sample when only partial prior information about cell type composition is available. We demonstrate the utility of MixChIP by analyzing ChIP-seq data from two cell lines which we artificially mix to generate (simulated) heterogeneous samples and by analyzing ChIP-seq data from breast cancer patients measuring oestrogen receptor (ER) binding in primary breast cancer tissues. We show that MixChIP is more accurate in detecting TF binding sites from multiple heterogeneous ChIP-seq samples than the standard methods which do not account for sample heterogeneity.ConclusionsOur results show that MixChIP can estimate cell-type proportions and identify cell type specific TF binding sites from heterogeneous ChIP-seq samples. Thus, MixChIP can be an invaluable tool in analyzing heterogeneous ChIP-seq samples, such as those originating from cancer studies. R implementation is available at http://research.ics.aalto.fi/csb/software/mixchip/.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0834-3) contains supplementary material, which is available to authorized users.

Fracture Optimization in the Valdemar Field Offshore Denmark

This article, written by JPT Technology Editor Chris Carpenter, contains highlights of paper SPE 170981, “Fracture Optimization Reduces Completion Cost While Improving Well Productivity in the Valdemar Field Offshore Denmark,” by Dario Stemberger, SPE, Maersk Oil, and Pedro Saldungaray, SPE, and Terry Palisch, SPE, Carbo Ceramics, prepared for the 2014 SPE Annual Technical Conference and Exhibition, Amsterdam, 27–29 October. The paper has not been peer reviewed. The Valdemar field contains a target reservoir that is a Lower Cretaceous “dirty chalk” containing up to 25% insoluble fines, porosity greater than 20%, and permeability below 0.5 md. Stimulations on several wells showed suboptimal production rates, which led to the conclusion that the Lower Cretaceous was not economically producible. An intensive study was therefore carried out to evaluate all aspects of the fracture design and implementation. This paper focuses on the aspects of proppant selection and adequate fracture-conductivity placement, with the goal of improving well productivity and cumulative recovery. Completion Optimization The Valdemar field is located in the Danish sector of the North Sea. The reservoir is characterized by a heterogeneous sequence of argillaceous chalk with thin beds of marl and claystone. The Lower Cretaceous reservoir is subdivided into 14 reservoir units on the basis of nanopaleontology and sequence stratigraphy. Because of the Valdemar field’s suboptimal production rates, an intensive study was carried out in 2008. Numerous experts were invited to view data, perform simulations, and offer recommendations. Eleven key items were identified as areas of potential improvement and are detailed further in the complete paper: Improve the accuracy of treatment displacements. Implement aggressive fracturing-fluid-breaker designs. Improve fracture conductivity by use of resieved sand. Introduce real-time data acquisition and modeling. Enhance interpretation of minifracture analysis. Gather pressure data for afterclosure analysis. Minimize total fluids injected. Assess the use of ceramic screened sliding sleeves for proppant-flowback control. Supervise well cleanup. Institute quality-control procedure for completion brine. Introduce ceramic proppants for fracture-conductivity enhancement. A study by a third-party consultant was conducted to determine the optimum fracture design. The study concluded that, for various reasons, the fractures were conductivity-limited, and that larger proppant was needed to improve effective fracture conductivity. This recommendation was furthered by implementing ceramic proppant, a process discussed in detail in the complete paper.

A novel framework for analyzing somatic copy number aberrations and tumor subclones for paired heterogeneous tumor samples.

Application of the Next generation sequencing (NGS) technology has demonstrated that most tumor samples exhibit intra-tumor heterogeneity. Here we proposed SAPPH (Somatic Aberrations Prediction for Paired Heterogeneous tumor samples), as a new method for estimating tumor somatic copy number aberrations as well as inferring tumor subclone proportions from heterogeneous tumor sequencing data. This method is based on CBS and local proportion clustering strategy. When SAPPH is applied on simulated tumor samples, the agreement between the results analyzed by SAPPH and the sequencing signals suggests that SAPPH can find the solution to best fit the signal distributions. We benchmark the performance of SAPPH and show that it outperforms existing method in estimating tumor copy number aberrations.

Cooperative routing with video complexity for heterogeneous motion-level streaming

Cooperative relay is a promising technique that can improve network capacity in multi-hop wireless networks. However, conventional video streaming schemes on cooperative relay networks do not consider the video complexity of each video sequence. In this paper, we develop and experimentally evaluate a video streaming scheme that considers video complexity over a cooperative multi-hop relay network. We first develop a video distortion model taking into account the video complexity of the video sequences. Then, we propose a flow-routing algorithm for heterogeneous motion-level video streams in multi-hop cooperative networks. To evaluate the video routing performance for heterogeneous motion-level video sequences, we conduct experimental simulations with the proposed routing algorithm and a video distortion model. Numerical results show that network performance improves when video sequences are routed while considering heterogeneous motion levels to maximize the minimum peak signal-to-noise ratio (PSNR) value for the video sessions. The simulation results also show that the adoption of cooperative relays and a hop-count limitation can also improve the routing performance of video streams.

Evolutionary progress in the functions of metallothioneins in the ever changing ecosystems

Metallothioneins (MTs) exist in various org anisms ranging from some prokaryotes to eukaryotes and mammals. MTs are low molecular weight proteins (MW ranging from 500 to 14000 Da), highly rich in cysteine residues and effectively bind with metals. MTs have the capacity to bind both physiological (such as zinc, copper, selenium) and xenobiotic (such as cadmium, mercury, silver, arsenic) heavy metals through the thiol group of its cysteine residues, which represent nearly 30 % of its constituent amino acid residues. Their combination with heavy metals gives rise to metal-thiolate clusters. It has been suspected that the presence of cysteine in MT is necessary for its functioning and that MT itself is essential for life, modulating complex diseases and the immune system. All different types of MTs are classified with respect to so many factors mainly in groups I and II. There are four main distinguished sub families of the mammalian MT gene families; MT-1 (subtypes A, B, E, F, G, H, L, M, X), MT-2, MT-3, MT-4. They are synthesised primarily in the liver and kidneys. Their production is dependent on availability of the dietary minerals, as zinc, copper and selenium, and the amino acids histidine and cysteine. The rise of these sub families can be attributed to the different functions fulfilled by them. The absence of one defined primary common function could certainly be the reason for serial duplications that gave rise to the respective isoforms. The evolution of MT has been so important to science that they have been considered valid biomarkers in medicine and environmental studies. MT is not limited to the human system, it has also been found in other mammals of the animal kingdom vertebrates (such as the chicken, Gallus gallus, or the mammalian Mus musculus), in higher plants (such as Pisum sativum, Triticum durum, Zea mays, Quercus suber), in protozoa (ex. the ciliate Tetrahymena genera), in yeast (such as Saccharomyces cerevisiae, Candida albicans), in invertebrates (such as the nematode Caenorhabditis elegans, the insect Drosophila melanogaster, the mollusc Mytilus edulis, or the echinoderm Strongylocentrotus purpuratus and in many prokaryotes (such as the cyanobacteria Syneccococus spp). The MTs from this diverse taxonomic range represent a high- heterogeneity sequence (regarding molecular weight and number and distribution of Cys residues) and do not show general homology; in spite of this, homology is found inside some taxonomic groups (such as vertebrate MTs). In this review, we will be looking at the evolution of MTs in respective organisms and the different roles they perform in each of their respective locations in these organisms. We will specifically look at the following factors; evolution of the genetic constitution of MTs and their structural composition and functions.

Reconciliation of hydroclimate sequences from the Chinese Loess Plateau and low-latitude East Asian Summer Monsoon regions over the past 14,500years

We discuss replicated stalagmite δ18O records with interannual-to-multidecadal resolution from Lianhua Cave on the Chinese Loess Plateau to illustrate the precipitation history of the East Asian Summer Monsoon (EASM) region over the last 14.5 thousand years (ka BP, before 1950 CE, hereafter), and to re-evaluate the inconsistency in the proxy-inferred palaeoclimate time series in northern China. Agreement between the stalagmite δ18O from Lianhua and other caves from central-southern China indicates that regional climate changes after the Last Glacial were concurrent across mainland China, indicating that insolation was the primary factor controlling the evolution of the Asian Summer Monsoon (ASM). The stalagmite 18O enrichment of 2.5‰ in the Younger Dryas and 1.7‰ during the 8.2-ka BP event in Lianhua were larger than those in caves from central and southern China. The evidence suggests that different meridional responses of weak precipitation conditions in the ASM realm occurred during these two abrupt events, driven by high-latitude forcing in the Northern Hemisphere. The heterogeneous hydroclimate sequences in northern China inferred from different natural archives are most likely attributable to the complexity of the formations and/or some chronological uncertainty.

Mining Signatures from Event Sequences

This paper proposes a novel secular knowledge representation and learning framework to proposed large- scale secular signature mining of longitudinal heterogeneous occasional data. The framework allows the presentation, extra4ction, and mining of high order latent occasion event structure and relationships between single and many sequences. The prescribed data representation maps the heterogeneous sequences to a image by encoding occasions as a structured spatial-secular shape process. We have suggested clinical assessment for naked interactive knowledge discovery in large electronic health record databases.

RVD2: an ultra-sensitive variant detection model for low-depth heterogeneous next-generation sequencing data.

Motivation: Next-generation sequencing technology is increasingly being used for clinical diagnostic tests. Clinical samples are often genomically heterogeneous due to low sample purity or the presence of genetic subpopulations. Therefore, a variant calling algorithm for calling low-frequency polymorphisms in heterogeneous samples is needed.Results: We present a novel variant calling algorithm that uses a hierarchical Bayesian model to estimate allele frequency and call variants in heterogeneous samples. We show that our algorithm improves upon current classifiers and has higher sensitivity and specificity over a wide range of median read depth and minor allele fraction. We apply our model and identify 15 mutated loci in the PAXP1 gene in a matched clinical breast ductal carcinoma tumor sample; two of which are likely loss-of-heterozygosity events.Availability and implementation: http://genomics.wpi.edu/rvd2/.Contact: pjflaherty@wpi.eduSupplementary information: Supplementary data are available at Bioinformatics online.

Insights into the Origin of Clostridium botulinum Strains: Evolution of Distinct Restriction Endonuclease Sites in rrs (16S rRNA gene).

Diversity analysis of Clostridium botulinum strains is complicated by high microheterogeneity caused by the presence of 9-22 copies of rrs (16S rRNA gene). The need is to mine genetic markers to identify very closely related strains. Multiple alignments of the nucleotide sequences of the 212 rrs of 13 C. botulinum strains revealed intra- and inter-genomic heterogeneity. Low intragenomic heterogeneity in rrs was evident in strains 230613, Alaska E43, Okra, Eklund 17B, Langeland, 657, Kyoto, BKT015925, and Loch Maree. The most heterogenous rrs sequences were those of C. botulinum strains ATCC 19397, Hall, H04402065, and ATCC 3502. In silico restriction mapping of these rrs sequences was observable with 137 type II Restriction endonucleases (REs). Nucleotide changes (NC)at these RE sites resulted in appearance of distinct and additional sites, and loss in certain others. De novo appearances of RE sites due to NC were recorded at different positions in rrs gene. A nucleotide transition A>G in rrs of C. botulinum Loch Maree and 657 resulted in the generation of 4 and 10 distinct RE sites, respectively. Transitions A>G, G>A, and T>C led to the loss of RE sites. A perusal of the entire NC and in silico RE mapping of rrs of C. botulinum strains provided insights into their evolution. Segregation of strains on the basis of RE digestion patterns of rrs was validated by the cladistic analysis involving six house keeping genes: dnaN, gyrB, metG, prfA, pyrG, and Rho.

Bi-criteria appointment scheduling of patients with heterogeneous service sequences

This article addresses the challenges of scheduling patients with stochastic service times and heterogeneous service sequences in multi-stage facilities, while considering the availability and compatibility of resources with presence of a variety of patient types. The proposed method departs from existing literature by optimizing the scheduling of patients by integrating mathematical programming, simulation, and multiobjective tabu search methods to achieve our bi-objectives of minimizing the waiting time of patients and the completion time of the facility. Through intensive testing, the performance of the proposed approach is analyzed in terms of the solution quality and computation time, and is compared with the performance of the well-known method, Non-Dominated Sorting Genetic Algorithm (NSGA-II). The proposed method is then applied to actual data of a case study operating department in a major Canadian hospital and promising results have been observed. Based on this study, insights are provided for practitioners.

GlycoMine: a machine learning-based approach for predicting N-, C- and O-linked glycosylation in the human proteome.

Glycosylation is a ubiquitous type of protein post-translational modification (PTM) in eukaryotic cells, which plays vital roles in various biological processes (BPs) such as cellular communication, ligand recognition and subcellular recognition. It is estimated that >50% of the entire human proteome is glycosylated. However, it is still a significant challenge to identify glycosylation sites, which requires expensive/laborious experimental research. Thus, bioinformatics approaches that can predict the glycan occupancy at specific sequons in protein sequences would be useful for understanding and utilizing this important PTM. In this study, we present a novel bioinformatics tool called GlycoMine, which is a comprehensive tool for the systematic in silico identification of C-linked, N-linked, and O-linked glycosylation sites in the human proteome. GlycoMine was developed using the random forest algorithm and evaluated based on a well-prepared up-to-date benchmark dataset that encompasses all three types of glycosylation sites, which was curated from multiple public resources. Heterogeneous sequences and functional features were derived from various sources, and subjected to further two-step feature selection to characterize a condensed subset of optimal features that contributed most to the type-specific prediction of glycosylation sites. Five-fold cross-validation and independent tests show that this approach significantly improved the prediction performance compared with four existing prediction tools: NetNGlyc, NetOGlyc, EnsembleGly and GPP. We demonstrated that this tool could identify candidate glycosylation sites in case study proteins and applied it to identify many high-confidence glycosylation target proteins by screening the entire human proteome. The webserver, Java Applet, user instructions, datasets, and predicted glycosylation sites in the human proteome are freely available at http://www.structbioinfor.org/Lab/GlycoMine/. Jiangning.Song@monash.edu or James.Whisstock@monash.edu or zhangyang@nwsuaf.edu.cn Supplementary data are available at Bioinformatics online.

Low-concentration initiator primers improve the amplification of gene targets with high sequence variability.

The amplification and detection of diverse strains of an infectious virus or bacteria, or variants within a gene family is important for both clinical and basic research but can be difficult using conventional PCR. This report describes and illustrates a novel closed-tube method for amplifying and characterizing heterogeneous target sequences using members of the CTX-M beta-lactamase gene family. Different subgroups of CTX-M genes exhibit low sequence identity, but accurate and efficient detection of these variants is critical because they all confer resistance to penicillin, cefotaxime, and other antibiotics of the beta-lactam class. The method combines a single pair of "thermodynamic consensus primers" (tcPrimers) with one or more "initiator primers" (iPrimers), added at low concentration (5-10 nM). Each iPrimer improves the initial amplification of one or more variants because it has fewer mismatches to its intended target than the more abundant tcPrimers. As a result of initial amplification, each heterogeneous sequence is shifted stepwise toward a better match with the tcPrimers. As soon as the tcPrimer hybridization takes place, amplification proceeds with high efficiency. The tcPrimer pairs can be designed for symmetric PCR or for Linear-After-The-Exponential (LATE)-PCR. LATE-PCR offers the advantage of generating single-stranded DNA that can be characterized for different gene variants in the same closed tube, using low-temperature mismatch-tolerant fluorescent probes.