Analysing the similarity of proteins based on a new approach to empirical mode decomposition

The function of a protein can be partially determined by the information contained in its amino acid sequence. It can be assumed that proteins with similar amino acid sequences normally have closer functions. Hence analysing the similarity of proteins has become one of the most important areas of protein study. In this work, a layered comparison method is used to analyze the similarity of proteins. It is based on the empirical mode decomposition (EMD) method, and protein sequences are characterized by the intrinsic mode functions (IMFs). The similarity of proteins is studied with a new cross-correlation formula. It seems that the EMD method can be used to detect the functional relationship of two proteins. This kind of similarity method is a complement of traditional sequence similarity approaches which focus on the alignment of amino acids

Genome Sequence of Acinetobacter baumannii Strain A1, an Early Example of Antibiotic-Resistant Global Clone 1

Acinetobacter baumannii isolate A1 was recovered in the United Kingdom in 1982 and belongs to global clone 1 (GC1). Here, we present its complete 3.91-Mbp genome sequence, generated via a combination of short-read sequencing (Illumina), long-read sequencing (PacBio), and manual finishing.

Fixing the alignment: An exploration of budgeting practices in the home

Budgeting is an important means of controlling ones finances and reducing debt. This paper outlines our work towards designing more user centred technology for individual and household budgeting. Based on an ethnographically informed study with 15 participants, we highlight a misalignment between people's actual budgeting practices and those supported by off-the-shelf budgeting aids. In addressing this misalignment we outline three tenets that may be incorporated into future work in this area. These include (1) catering for the different phases of engagement with technology; (2) catering for the practices of hiding and limiting access to money, and; (3) integrating materiality into technical solutions.

Quantitative genetic modeling of lateral ventricular shape and volume using multi-atlas fluid image alignment in twins

Despite substantial progress in measuring the 3D profile of anatomical variations in the human brain, their genetic and environmental causes remain enigmatic. We developed an automated system to identify and map genetic and environmental effects on brain structure in large brain MRI databases . We applied our multi-template segmentation approach ("Multi-Atlas Fluid Image Alignment") to fluidly propagate hand-labeled parameterized surface meshes into 116 scans of twins (60 identical, 56 fraternal), labeling the lateral ventricles. Mesh surfaces were averaged within subjects to minimize segmentation error. We fitted quantitative genetic models at each of 30,000 surface points to measure the proportion of shape variance attributable to (1) genetic differences among subjects, (2) environmental influences unique to each individual, and (3) shared environmental effects. Surface-based statistical maps revealed 3D heritability patterns, and their significance, with and without adjustments for global brain scale. These maps visualized detailed profiles of environmental versus genetic influences on the brain, extending genetic models to spatially detailed, automatically computed, 3D maps.

Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer's disease

We developed and validated a new method to create automated 3D parametric surface models of the lateral ventricles in brain MRI scans, providing an efficient approach to monitor degenerative disease in clinical studies and drug trials. First, we used a set of parameterized surfaces to represent the ventricles in four subjects' manually labeled brain MRI scans (atlases). We fluidly registered each atlas and mesh model to MRIs from 17 Alzheimer's disease (AD) patients and 13 age- and gender-matched healthy elderly control subjects, and 18 asymptomatic ApoE4-carriers and 18 age- and gender-matched non-carriers. We examined genotyped healthy subjects with the goal of detecting subtle effects of a gene that confers heightened risk for Alzheimer's disease. We averaged the meshes extracted for each 3D MR data set, and combined the automated segmentations with a radial mapping approach to localize ventricular shape differences in patients. Validation experiments comparing automated and expert manual segmentations showed that (1) the Hausdorff labeling error rapidly decreased, and (2) the power to detect disease- and gene-related alterations improved, as the number of atlases, N, was increased from 1 to 9. In surface-based statistical maps, we detected more widespread and intense anatomical deficits as we increased the number of atlases. We formulated a statistical stopping criterion to determine the optimal number of atlases to use. Healthy ApoE4-carriers and those with AD showed local ventricular abnormalities. This high-throughput method for morphometric studies further motivates the combination of genetic and neuroimaging strategies in predicting AD progression and treatment response. © 2007 Elsevier Inc. All rights reserved.

The sequence: Inside the race for the human genome

The human genome project was a grand scientific enterprise which attracted both hyperbole and ridicule alike. The project was lauded as “the moon shot of the life sciences”, the “holy grail of man”, “the code of codes”, and “the book of life”. Such rhetoric has also received scorn. President George Bush senior managed to deflate the pretensions of the project with the accidental slip that it was the “human gnome initiative”. In The Sequence, Kevin Davies seeks to go beyond such metaphors, and provide a candid and honest account of the race of the human genome project. The author is indebted to the authoritative book The Gene Wars, which considered the early struggles over the human genome project. Robert Cook-Deegan observes that there was initially much debate over whether there should be a Human Genome Project at all: The debate became one of “big” science versus “small” science. The reliance on systematic technology development and goal-directed gene-mapping efforts presaged a new style for biology, one that elicited excitement from those attracted to whiz-bang technologies but drew gasps of revulsion from those who aspired to cultivate biology on a more modest scale and with decentralized organisation. The battle was, among other things, over whose vision would control the budget and which scientific aesthetic would prevail.

The new conquistadors: Patent law and expressed sequence tags

It's akin to the old Spanish, English and Portuguese explorers. They would take their boats until they found some edge of land, then they would go up and plant the flag of their king or queen. They didn't know what they'd discovered; how big it is, where it goes to - but they would claim it anyway. David Korn of the Association of American Medical Colleges This article analyses recent litigation over patent law and expressed sequence tags (ESTs). In the case of In re Fisher, the United States Court of Appeals for the Federal Circuit engaged in judicial consideration of the revised utility guidelines of the United States Patent and Trademark Office (USPTO). In this matter, the agricultural biotechnology company Monsanto sought to patent ESTs in maize plants. A patent examiner and the Board of Patent Appeals and Interferences had doubted whether the patent application was useful. Monsanto appealed against the rulings of the USPTO. A number of amicus curiae intervened in the matter in support of the USPTO - including Genentech, Affymetrix, Dow AgroSciences, Eli Lilly, the National Academy of Sciences, and the Association of American Medical Colleges. The majority of the Court of Appeals for the Federal Circuit supported the position of the USPTO, and rejected the patent application on the grounds of utility. The split decision highlighted institutional tensions over the appropriate thresholds for patent criteria - such as novelty, non-obviousness, and utility. The litigation raised larger questions about the definition of research tools, the incremental nature of scientific progress, and the role of patent law in innovation policy. The decision of In re Fisher will have significant ramifications for gene patents, in the wake of the human genome project. Arguably, the USPTO utility guidelines need to be reinforced by a tougher application of the standards of novelty and non-obviousness in respect of gene patents.

Complex Symbolic Sequence Encodings for Predictive Monitoring of Business Processes

This paper addresses the problem of predicting the outcome of an ongoing case of a business process based on event logs. In this setting, the outcome of a case may refer for example to the achievement of a performance objective or the fulfillment of a compliance rule upon completion of the case. Given a log consisting of traces of completed cases, given a trace of an ongoing case, and given two or more possible out- comes (e.g., a positive and a negative outcome), the paper addresses the problem of determining the most likely outcome for the case in question. Previous approaches to this problem are largely based on simple symbolic sequence classification, meaning that they extract features from traces seen as sequences of event labels, and use these features to construct a classifier for runtime prediction. In doing so, these approaches ignore the data payload associated to each event. This paper approaches the problem from a different angle by treating traces as complex symbolic sequences, that is, sequences of events each carrying a data payload. In this context, the paper outlines different feature encodings of complex symbolic sequences and compares their predictive accuracy on real-life business process event logs.

Genome sequence of marine bacterium idiomarina sp. strain 28-8, isolated from Korean ark shells

Idiomarina sp. strain 28-8 is an aerobic, Gram-negative, flagellar bacterium isolated from the bodies of ark shells (Scapharca broughtonii) collected from underwater sediments in Gangjin Bay, South Korea. Here, we present the draft genome sequence of Idiomarina sp. 28-8 (2,971,606 bp, with a G+C content of 46.9%), containing 2,795 putative coding sequences.

Mitochondrial DNA sequence analysis from multiple gene fragments reveals genetic heterogeneity of Crassostrea ariakensis in East Asia

The native Asian oyster, Crassostrea ariakensis is one of the most common and important Crassostrea species that occur naturally along the coast of East Asia. Molecular species diagnosis is a prerequisite for population genetic analysis of wild oyster populations because oyster species cannot be discriminated reliably using external morphological characters alone due to character ambiguity. To date there have been few phylogeographic studies of natural edible oyster populations in East Asia, in particular this is true of the common species in Korea C. ariakensis. We therefore assessed the levels and patterns of molecular genetic variation in East Asian wild populations of C. ariakensis from Korea, Japan, and China using DNA sequence analysis of five concatenated mtDNA regions namely; 16S rRNA, cytochrome oxidase I, cytochrome oxidase II, cytochrome oxidase III, and cytochrome b. Two divergent C. ariakensis clades were identified between southern China and remaining sites from the northern region. In addition, hierarchical AMOVA and pairwise UST analyses showed that genetic diversity was discontinuous among wild populations of C. ariakensis in East Asia. Biogeographical and historical sea level changes are discussed as potential factors that may have influenced the genetic heterogeneity of wild C. ariakensis stocks across this region.

Transferability of cupped oyster EST (Expressed Sequence Tag)-derived SNP (Single Nucleotide Polymorphism) markers to related crassostrea and ostrea species

Single nucleotide polymorphisms (SNPs) are widely acknowledged as the marker of choice for many genetic and genomic applications because they show co-dominant inheritance, are highly abundant across genomes and are suitable for high-throughput genotyping. Here we evaluated the applicability of SNP markers developed from Crassostrea gigas and C. virginica expressed sequence tags (ESTs) in closely related Crassostrea and Ostrea species. A total of 213 putative interspecific level SNPs were identified from re-sequencing data in six amplicons, yielding on average of one interspecific level SNP per seven bp. High polymorphism levels were observed and the high success rate of transferability show that genic EST-derived SNP markers provide an efficient method for rapid marker development and SNP discovery in closely related oyster species. The six EST-SNP markers identified here will provide useful molecular tools for addressing questions in molecular ecology and evolution studies including for stock analysis (pedigree monitoring) in related oyster taxa.

Knee alignment can help predict sedentary behaviour in children: a pilot study

AIM: The purpose of this pilot study was to introduce knee alignment as a potential predictor of sedentary activity levels in boys and girls. METHODS: Dual energy x-ray absorptiometry (DXA) and anthropometric assessment were conducted on 47 children (21 boys and 26 girls; 5-14 y) and their gender-matched parent. Body Mass Index (BMI) and abdominal-to-height ratio were calculated. Lower extremity alignment was determined by anatomic tibiofemoral angle (TFA) measurements from DXA images. Time spent in moderate-to-vigorous physical activity and sedentary activities were obtained from a parent-reported questionnaire. Stepwise multiple regression analyses identified anthropometric, musculoskeletal, and activity factors of parents and children for predicting total time spent in sedentary behaviour. RESULTS: Weight, total sedentary time of parents and TFA are moderate predictors of sedentary behaviour in children (R2=0.469). When stratifying for gender, TFA and total sedentary time of the parent, as well as waist circumference, are the most useful predictors of sedentary behaviour in boys (R2=0.648). However, weight is the only predictor of sedentary behaviour in girls (R2=0.479). CONCLUSION: Negative associations between TFA and sedentary behaviour indicate that even slight variations in musculoskeletal alignment may influence a child's motivation to be physically active. Although growth and development is complicated by many potentialities, this pilot study suggests that orthopaedic factors should also be considered when evaluating physical activity in children

Dissimilarities in alignment-free methods for phylogenetic analysis based on genomes

Whole genome sequences are generally accepted as excellent tools for studying evolutionary relationships. Due to the problems caused by the uncertainty in alignment, existing tools for phylogenetic analysis based on multiple alignments could not be directly applied to the whole-genome comparison and phylogenomic studies. There has been a growing interest in alignment-free methods for phylogenetic analysis using complete genome data. The “distances” used in these alignment-free methods are not proper distance metrics in the strict mathematical sense. In this study, we first review them in a more general frame — dissimilarity. Then we propose some new dissimilarities for phylogenetic analysis. Last three genome datasets are employed to evaluate these dissimilarities from a biological point of view.

Mixture models of nucleotide sequence evolution that account for heterogeneity in the substitution process across sites and across lineages

Molecular phylogenetic studies of homologous sequences of nucleotides often assume that the underlying evolutionary process was globally stationary, reversible, and homogeneous (SRH), and that a model of evolution with one or more site-specific and time-reversible rate matrices (e.g., the GTR rate matrix) is enough to accurately model the evolution of data over the whole tree. However, an increasing body of data suggests that evolution under these conditions is an exception, rather than the norm. To address this issue, several non-SRH models of molecular evolution have been proposed, but they either ignore heterogeneity in the substitution process across sites (HAS) or assume it can be modeled accurately using the distribution. As an alternative to these models of evolution, we introduce a family of mixture models that approximate HAS without the assumption of an underlying predefined statistical distribution. This family of mixture models is combined with non-SRH models of evolution that account for heterogeneity in the substitution process across lineages (HAL). We also present two algorithms for searching model space and identifying an optimal model of evolution that is less likely to over- or underparameterize the data. The performance of the two new algorithms was evaluated using alignments of nucleotides with 10 000 sites simulated under complex non-SRH conditions on a 25-tipped tree. The algorithms were found to be very successful, identifying the correct HAL model with a 75% success rate (the average success rate for assigning rate matrices to the tree's 48 edges was 99.25%) and, for the correct HAL model, identifying the correct HAS model with a 98% success rate. Finally, parameter estimates obtained under the correct HAL-HAS model were found to be accurate and precise. The merits of our new algorithms were illustrated with an analysis of 42 337 second codon sites extracted from a concatenation of 106 alignments of orthologous genes encoded by the nuclear genomes of Saccharomyces cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, S. castellii, S. kluyveri, S. bayanus, and Candida albicans. Our results show that second codon sites in the ancestral genome of these species contained 49.1% invariable sites, 39.6% variable sites belonging to one rate category (V1), and 11.3% variable sites belonging to a second rate category (V2). The ancestral nucleotide content was found to differ markedly across these three sets of sites, and the evolutionary processes operating at the variable sites were found to be non-SRH and best modeled by a combination of eight edge-specific rate matrices (four for V1 and four for V2). The number of substitutions per site at the variable sites also differed markedly, with sites belonging to V1 evolving slower than those belonging to V2 along the lineages separating the seven species of Saccharomyces. Finally, sites belonging to V1 appeared to have ceased evolving along the lineages separating S. cerevisiae, S. paradoxus, S. mikatae, S. kudriavzevii, and S. bayanus, implying that they might have become so selectively constrained that they could be considered invariable sites in these species.

The koala immunological toolkit: Sequence identification and comparison of key markers of the koala (Phascolarctos cinereus) immune response

The koala (Phascolarctos cinereus) is an Australian marsupial that continues to experience significant population declines. Infectious diseases caused by pathogens such as Chlamydia are proposed to have a major role. Very few species-specific immunological reagents are available, severely hindering our ability to respond to the threat of infectious diseases in the koala. In this study, we utilise data from the sequencing of the koala transcriptome to identify key immunological markers of the koala adaptive immune response and cytokines known to be important in the host response to chlamydial infection in other species. This report describes the identification and preliminary sequence analysis of (1) T lymphocyte glycoprotein markers (CD4, CD8); (2) IL-4, a marker for the Th2 response; (3) cytokines such as IL-6, IL-12 and IL-1β, that have been shown to have a role in chlamydial clearance and pathology in other hosts; and (4) the sequences for the koala immunoglobulins, IgA, IgG, IgE and IgM. These sequences will enable the development of a range of immunological reagents for understanding the koala’s innate and adaptive immune responses, while also providing a resource that will enable continued investigations into the origin and evolution of the marsupial immune system.