Markov models of aging: theory and practice

We review and structure some of the mathematical and statistical models that have been developed over the past half century to grapple with theoretical and experimental questions about the stochastic development of aging over the life course. We suggest that the mathematical models are in large part addressing the problem of partitioning the randomness in aging: How does aging vary between individuals, and within an individual over the lifecourse? How much of the variation is inherently related to some qualities of the individual, and how much is entirely random? How much of the randomness is cumulative, and how much is merely short-term flutter? We propose that recent lines of statistical inquiry in survival analysis could usefully grapple with these questions, all the more so if they were more explicitly linked to the relevant mathematical and biological models of aging. To this end, we describe points of contact among the various lines of mathematical and statistical research. We suggest some directions for future work, including the exploration of information-theoretic measures for evaluating components of stochastic models as the basis for analyzing experiments and anchoring theoretical discussions of aging.

Bayesian parameter estimation for latent Markov random fields and social networks

Undirected graphical models are widely used in statistics, physics and machine vision. However Bayesian parameter estimation for undirected models is extremely challenging, since evaluation of the posterior typically involves the calculation of an intractable normalising constant. This problem has received much attention, but very little of this has focussed on the important practical case where the data consists of noisy or incomplete observations of the underlying hidden structure. This paper specifically addresses this problem, comparing two alternative methodologies. In the first of these approaches particle Markov chain Monte Carlo (Andrieu et al., 2010) is used to efficiently explore the parameter space, combined with the exchange algorithm (Murray et al., 2006) for avoiding the calculation of the intractable normalising constant (a proof showing that this combination targets the correct distribution in found in a supplementary appendix online). This approach is compared with approximate Bayesian computation (Pritchard et al., 1999). Applications to estimating the parameters of Ising models and exponential random graphs from noisy data are presented. Each algorithm used in the paper targets an approximation to the true posterior due to the use of MCMC to simulate from the latent graphical model, in lieu of being able to do this exactly in general. The supplementary appendix also describes the nature of the resulting approximation.

The integration of proteomics and systems approaches to map regulatory mechanisms underpinning platelet function.

Platelets in the circulation are triggered by vascular damage to activate, aggregate and form a thrombus that prevents excessive blood loss. Platelet activation is stringently regulated by intracellular signalling cascades, which when activated inappropriately lead to myocardial infarction and stroke. Strategies to address platelet dysfunction have included proteomics approaches which have lead to the discovery of a number of novel regulatory proteins of potential therapeutic value. Global analysis of platelet proteomes may enhance the outcome of these studies by arranging this information in a contextual manner that recapitulates established signalling complexes and predicts novel regulatory processes. Platelet signalling networks have already begun to be exploited with interrogation of protein datasets using in silico methodologies that locate functionally feasible protein clusters for subsequent biochemical validation. Characterization of these biological systems through analysis of spatial and temporal organization of component proteins is developing alongside advances in the proteomics field. This focused review highlights advances in platelet proteomics data mining approaches that complement the emerging systems biology field. We have also highlighted nucleated cell types as key examples that can inform platelet research. Therapeutic translation of these modern approaches to understanding platelet regulatory mechanisms will enable the development of novel anti-thrombotic strategies.

A Web Map Service implementation for the visualization of multidimensional gridded environmental data

We describe ncWMS, an implementation of the Open Geospatial Consortium’s Web Map Service (WMS) specification for multidimensional gridded environmental data. ncWMS can read data in a large number of common scientific data formats – notably the NetCDF format with the Climate and Forecast conventions – then efficiently generate map imagery in thousands of different coordinate reference systems. It is designed to require minimal configuration from the system administrator and, when used in conjunction with a suitable client tool, provides end users with an interactive means for visualizing data without the need to download large files or interpret complex metadata. It is also used as a “bridging” tool providing interoperability between the environmental science community and users of geographic information systems. ncWMS implements a number of extensions to the WMS standard in order to fulfil some common scientific requirements, including the ability to generate plots representing timeseries and vertical sections. We discuss these extensions and their impact upon present and future interoperability. We discuss the conceptual mapping between the WMS data model and the data models used by gridded data formats, highlighting areas in which the mapping is incomplete or ambiguous. We discuss the architecture of the system and particular technical innovations of note, including the algorithms used for fast data reading and image generation. ncWMS has been widely adopted within the environmental data community and we discuss some of the ways in which the software is integrated within data infrastructures and portals.

An effective approach for land-cover classification from airborne lidar fused with co-registered data

Airborne lidar provides accurate height information of objects on the earth and has been recognized as a reliable and accurate surveying tool in many applications. In particular, lidar data offer vital and significant features for urban land-cover classification, which is an important task in urban land-use studies. In this article, we present an effective approach in which lidar data fused with its co-registered images (i.e. aerial colour images containing red, green and blue (RGB) bands and near-infrared (NIR) images) and other derived features are used effectively for accurate urban land-cover classification. The proposed approach begins with an initial classification performed by the Dempster–Shafer theory of evidence with a specifically designed basic probability assignment function. It outputs two results, i.e. the initial classification and pseudo-training samples, which are selected automatically according to the combined probability masses. Second, a support vector machine (SVM)-based probability estimator is adopted to compute the class conditional probability (CCP) for each pixel from the pseudo-training samples. Finally, a Markov random field (MRF) model is established to combine spatial contextual information into the classification. In this stage, the initial classification result and the CCP are exploited. An efficient belief propagation (EBP) algorithm is developed to search for the global minimum-energy solution for the maximum a posteriori (MAP)-MRF framework in which three techniques are developed to speed up the standard belief propagation (BP) algorithm. Lidar and its co-registered data acquired by Toposys Falcon II are used in performance tests. The experimental results prove that fusing the height data and optical images is particularly suited for urban land-cover classification. There is no training sample needed in the proposed approach, and the computational cost is relatively low. An average classification accuracy of 93.63% is achieved.

Integration of retrotransposons-based markers in a linkage map of barley

A deeper understanding of random markers is important if they are to be employed for a range of objectives. The sequence specific amplified polymorphism (S-SAP) technique is a powerful genetic analysis tool which exploits the high copy number of retrotransposon long terminal repeats (LTRs) in the plant genome. The distribution and inheritance of S-SAP bands in the barley genome was studied using the Steptoe × Morex (S × M) double haploid (DH) population. Six S-SAP primer combinations generated 98 polymorphic bands, and map positions were assigned to all but one band. Eight putative co-dominant loci were detected, representing 16 of the mapped markers. Thus at least 81 of the mapped S-SAP loci were dominant. The markers were distributed along all of the seven chromosomes and a tendency to cluster was observed. The distribution of S-SAP markers over the barley genome concurred with the knowledge of the high copy number of retrotransposons in plants. This experiment has demonstrated the potential for the S-SAP technique to be applied in a range of analyses such as genetic fingerprinting, marker assisted breeding, biodiversity assessment and phylogenetic analyses.

Construction of a Festuca pratensis BAC library for map-based cloning in Festulolium substitution lines

Introgression in Festulolium is a potentially powerful tool to isolate genes for a large number of traits which differ between Festuca pratensis Huds. and Lolium perenne L. Not only are hybrids between the two species fertile, but the two genomes can be distinguished by genomic in situ hybridisation and a high frequency of recombination occurs between homoeologous chromosomes and chromosome segments. By a programme of introgression and a series of backcrosses, L. perenne lines have been produced which contain small F. pratensis substitutions. This material is a rich source of polymorphic markers targeted towards any trait carried on the F. pratensis substitution not observed in the L. perenne background. We describe here the construction of an F. pratensis BAC library, which establishes the basis of a map-based cloning strategy in L. perenne. The library contains 49,152 clones, with an average insert size of 112 kbp, providing coverage of 2.5 haploid genome equivalents. We have screened the library for eight amplified fragment length polymorphism (AFLP) derived markers known to be linked to an F. pratensis gene introgressed into L. perenne and conferring a staygreen phenotype as a consequence of a mutation in primary chlorophyll catabolism. While for four of the markers it was possible to identify bacterial artificial chromosome (BAC) clones, the other four AFLPs were too repetitive to enable reliable identification of locus-specific BACs. Moreover, when the four BACs were partially sequenced, no obvious coding regions could be identified. This contrasted to BACs identified using cDNA sequences, when multiple genes were identified on the same BAC.

Business cycle asymmetries: characterisation and testing based on Markov-switching autoregressions

Tests for business cycle asymmetries are developed for Markov-switching autoregressive models. The tests of deepness, steepness, and sharpness are Wald statistics, which have standard asymptotics. For the standard two-regime model of expansions and contractions, deepness is shown to imply sharpness (and vice versa), whereas the process is always nonsteep. Two and three-state models of U.S. GNP growth are used to illustrate the approach, along with models of U.S. investment and consumption growth. The robustness of the tests to model misspecification, and the effects of regime-dependent heteroscedasticity, are investigated.

Threshold autoregressive and Markov switching models: an application to commercial real estate

Although financial theory rests heavily upon the assumption that asset returns are normally distributed, value indices of commercial real estate display significant departures from normality. In this paper, we apply and compare the properties of two recently proposed regime switching models for value indices of commercial real estate in the US and the UK, both of which relax the assumption that observations are drawn from a single distribution with constant mean and variance. Statistical tests of the models' specification indicate that the Markov switching model is better able to capture the non-stationary features of the data than the threshold autoregressive model, although both represent superior descriptions of the data than the models that allow for only one state. Our results have several implications for theoretical models and empirical research in finance.

Noisy Monte Carlo: convergence of Markov chains with approximate transition kernels

Monte Carlo algorithms often aim to draw from a distribution π by simulating a Markov chain with transition kernel P such that π is invariant under P. However, there are many situations for which it is impractical or impossible to draw from the transition kernel P. For instance, this is the case with massive datasets, where is it prohibitively expensive to calculate the likelihood and is also the case for intractable likelihood models arising from, for example, Gibbs random fields, such as those found in spatial statistics and network analysis. A natural approach in these cases is to replace P by an approximation Pˆ. Using theory from the stability of Markov chains we explore a variety of situations where it is possible to quantify how ’close’ the chain given by the transition kernel Pˆ is to the chain given by P . We apply these results to several examples from spatial statistics and network analysis.

Hidden Markov analysis describes dive patterns in semiaquatic animals

Existing methods of dive analysis, developed for fully aquatic animals, tend to focus on frequency of behaviors rather than transitions between them. They, therefore, do not account for the variability of behavior of semiaquatic animals, and the switching between terrestrial and aquatic environments. This is the first study to use hidden Markov models (HMM) to divide dives of a semiaquatic animal into clusters and thus identify the environmental predictors of transition between behavioral modes. We used 18 existing data sets of the dives of 14 American mink (Neovison vison) fitted with time-depth recorders in lowland England. Using HMM, we identified 3 behavioral states (1, temporal cluster of dives; 2, more loosely aggregated diving within aquatic activity; and 3, terminal dive of a cluster or a single, isolated dive). Based on the higher than expected proportion of dives in State 1, we conclude that mink tend to dive in clusters. We found no relationship between temperature and the proportion of dives in each state or between temperature and the rate of transition between states, meaning that in our study area, mink are apparently not adopting different diving strategies at different temperatures. Transition analysis between states has shown that there is no correlation between ambient temperature and the likelihood of mink switching from one state to another, that is, changing foraging modes. The variables provided good discrimination and grouped into consistent states well, indicating promise for further application of HMM and other state transition analyses in studies of semiaquatic animals.

A land cover map of Latin America and the Caribbean in the framework of the SERENA project

Land cover maps at different resolutions and mapping extents contribute to modeling and support decision making processes. Because land cover affects and is affected by climate change, it is listed among the 13 terrestrial essential climate variables. This paper describes the generation of a land cover map for Latin America and the Caribbean (LAC) for the year 2008. It was developed in the framework of the project Latin American Network for Monitoring and Studying of Natural Resources (SERENA), which has been developed within the GOFC-GOLD Latin American network of remote sensing and forest fires (RedLaTIF). The SERENA land cover map for LAC integrates: 1) the local expertise of SERENA network members to generate the training and validation data, 2) a methodology for land cover mapping based on decision trees using MODIS time series, and 3) class membership estimates to account for pixel heterogeneity issues. The discrete SERENA land cover product, derived from class memberships, yields an overall accuracy of 84% and includes an additional layer representing the estimated per-pixel confidence. The study demonstrates in detail the use of class memberships to better estimate the area of scarce classes with a scattered spatial distribution. The land cover map is already available as a printed wall map and will be released in digital format in the near future. The SERENA land cover map was produced with a legend and classification strategy similar to that used by the North American Land Change Monitoring System (NALCMS) to generate a land cover map of the North American continent, that will allow to combine both maps to generate consistent data across America facilitating continental monitoring and modeling

Generation and analysis of the 2005 land cover map for Mexico using 250m MODIS data

Land cover plays a key role in global to regional monitoring and modeling because it affects and is being affected by climate change and thus became one of the essential variables for climate change studies. National and international organizations require timely and accurate land cover information for reporting and management actions. The North American Land Change Monitoring System (NALCMS) is an international cooperation of organizations and entities of Canada, the United States, and Mexico to map land cover change of North America's changing environment. This paper presents the methodology to derive the land cover map of Mexico for the year 2005 which was integrated in the NALCMS continental map. Based on a time series of 250 m Moderate Resolution Imaging Spectroradiometer (MODIS) data and an extensive sample data base the complexity of the Mexican landscape required a specific approach to reflect land cover heterogeneity. To estimate the proportion of each land cover class for every pixel several decision tree classifications were combined to obtain class membership maps which were finally converted to a discrete map accompanied by a confidence estimate. The map yielded an overall accuracy of 82.5% (Kappa of 0.79) for pixels with at least 50% map confidence (71.3% of the data). An additional assessment with 780 randomly stratified samples and primary and alternative calls in the reference data to account for ambiguity indicated 83.4% overall accuracy (Kappa of 0.80). A high agreement of 83.6% for all pixels and 92.6% for pixels with a map confidence of more than 50% was found for the comparison between the land cover maps of 2005 and 2006. Further wall-to-wall comparisons to related land cover maps resulted in 56.6% agreement with the MODIS land cover product and a congruence of 49.5 with Globcover.

A SNP-based consensus genetic map for synteny-based trait targeting in faba bean (Vicia faba L.)

Faba bean (Vicia faba L.) is a globally important nitrogen-fixing legume, which is widely grown in a diverse range of environments. In this work, we mine and validate a set of 845 SNPs from the aligned transcriptomes of two contrasting inbred lines. Each V. faba SNP is assigned by BLAST analysis to a single Medicago orthologue. This set of syntenically anchored polymorphisms were then validated as individual KASP assays, classified according to their informativeness and performance on a panel of 37 inbred lines, and the best performing 757 markers used to genotype six mapping populations. The six resulting linkage maps were merged into a single consensus map on which 687 SNPs were placed on six linkage groups, each presumed to correspond to one of the six V. faba chromosomes. This sequence-based consensus map was used to explore synteny with the most closely-related crop species, lentil, and the most closely related fully sequenced genome, Medicago. Large tracts of uninterrupted colinearity were found between faba bean and Medicago, making it relatively straightforward to predict gene content and order in mapped genetic interval. As a demonstration of this, we mapped a flower colour gene to a 2 cM interval of Vf chromosome 2 which was highly collinear with Mt3. The obvious candidate gene from 77 gene models in the collinear Medicago chromosome segment was the previously characterized MtWD40-1 gene (Mt3g092830, Mt3g092840) controlling anthocyanin production in Medicago and re-sequencing of the Vf orthologue showed a putative causative deletion of the entire 5’ end of the gene.

Decomposition of surface electromyographic signal using Hidden Markov Model

The detection of physiological signals from the motor system (electromyographic signals) is being utilized in the practice clinic to guide the therapist in a more precise and accurate diagnosis of motor disorders. In this context, the process of decomposition of EMG (electromyographic) signals that includes the identification and classification of MUAP (Motor Unit Action Potential) of a EMG signal, is very important to help the therapist in the evaluation of motor disorders. The EMG decomposition is a complex task due to EMG features depend on the electrode type (needle or surface), its placement related to the muscle, the contraction level and the health of the Neuromuscular System. To date, the majority of researches on EMG decomposition utilize EMG signals acquired by needle electrodes, due to their advantages in processing this type of signal. However, relatively few researches have been conducted using surface EMG signals. Thus, this article aims to contribute to the clinical practice by presenting a technique that permit the decomposition of surface EMG signal via the use of Hidden Markov Models. This process is supported by the use of differential evolution and spectral clustering techniques. The developed system presented coherent results in: (1) identification of the number of Motor Units actives in the EMG signal; (2) presentation of the morphological patterns of MUAPs in the EMG signal; (3) identification of the firing sequence of the Motor Units. The model proposed in this work is an advance in the research area of decomposition of surface EMG signals.