Li Su with Michael J. Daniels (MRC Biostatistics Unit)
Bayesian modeling of the covariance structure for irregular longitudinal data using the partial autocorrelation function
Abstract: In long-term follow-up studies, irregular longitudinal data are observed when individuals are assessed repeatedly over time but at uncommon and irregularly spaced time points. Modeling the covariance structure for this type of data is challenging, as it requires specification of a covariance function that is positive definite. Moreover, in certain settings, careful modeling of the covariance structure for irregular longitudinal data can be crucial in order to ensure no bias arises in the mean structure. Two common settings where this occurs are studies with ‘outcome-dependent follow-up’ and studies with ‘ignorable missing data’. ‘Outcome-dependent follow-up’ occurs when individuals with a history of poor health outcomes had more follow-up measurements, and the intervals between the repeated measurements were shorter. When the follow-up time process only depends on previous outcomes, likelihood-based methods can still provide consistent estimates of the regression parameters, given that both the mean and covariance structures of the irregular longitudinal data are correctly specified and no model for the follow-up time process is required. For ‘ignorable missing data’, the missing data mechanism does not need to be specified, but valid likelihood-based inference requires correct specification of the covariance structure. In both cases, flexible modeling approaches for the covariance structure are essential. In this work*, we develop a flexible approach to modeling the covariance structure for irregular continuous longitudinal data using the partial autocorrelation function and the variance function. In particular, we propose semiparametric non-stationary partial autocorrelation function models, which do not suffer from complex positive definiteness restrictions like the autocorrelation function. We describe a Bayesian approach, discuss computational issues, and apply the proposed methods to CD4 count data from a pediatric AIDS clinical trial.
*Details can be found in the paper published in Statistics in Medicine 2015, 34, 2004–2018.

Ewan Cameron (Oxford, Dept of Zoology)

Progress and (Statistical) Challenges in Malariology

Abstract: In this talk I will describe some key statistical challenges faced by researchers aiming to quantify the burden of disease arising from Plasmodium falciparum malaria at the population level. These include covariate selection in the 'big data' setting, handling spatially-correlated residuals at scale, calibration of individual simulation models of disease transmission, and the embedding of continuous-time, discrete-state Markov Chain solutions within hierarchical Bayesian models. In each case I will describe the pragmatic solutions we've implemented to-date within the Malaria Atlas Project, and highlight more sophisticated solutions we'd like to have in the near-future if the right statistical methodology and computational tools can be identified and/or developed to this end.

References:

http://www.nature.com/nature/journal/v526/n7572/abs/nature15535.html

http://www.nature.com/ncomms/2015/150907/ncomms9170/full/ncomms9170.html

http://www.ncbi.nlm.nih.gov/pubmed/25890035

http://link.springer.com/article/10.1186/s12936-015-0984-9

Theresa Smith (CHICAS, Lancaster Medical School)

Modelling geo-located health data using spatio-temporal log-Gaussian Cox processes

Abstract: Health data with high spatial and temporal resolution are becoming more common, but there are several practical and computational challenges to using such data to study the relationships between disease risk and possible predictors. These difficulties include lack of measurements on individual-level covariates/exposures, integrating data measured on difference spatial and temporal units, and computational complexity.

In this talk, I outline strategies for jointly estimating systematic (i.e., parametric) trends in disease risk and assessing residual risk with spatio-temporal log-Gaussian Cox processes (LGCPs). In particular, I will present a Bayesian methods and MCMC tools for using spatio-temporal LGCPs to investigate the roles of environmental and socio-economic risk-factors in the incidence of Campylobacter in England.

Alan Gelfand (Duke, Dept of Statistical Science)

Title: Space and circular time log Gaussian Cox processes with application to crime event data

Abstract: We view the locations and times of a collection of crime events as a space-time point pattern. So, with either a nonhomogeneous Poisson process or with a more general Cox process, we need to specify a space-time intensity. For the latter, we need a random intensity which we model as a realization of a spatio-temporal log Gaussian process. In fact, we view time as circular, necessitating valid separable and nonseparable covariance functions over a bounded spatial region crossed with circular time. In addition, crimes are classified by crime type.

Furthermore, each crime event is marked by day of the year which we convert to day of the week. We present models to accommodate such data. Then, we extend the modeling to include the marks. Our specifications naturally take the form of hierarchical models which we t within a Bayesian framework. In this regard, we consider model comparison between the nonhomogeneous Poisson process and the log Gaussian Cox process. We also compare separable vs. nonseparable covariance specifications. 

Our motivating dataset is a collection of crime events for the city of San Francisco during the year 2012. Again, we have location, hour, day of the year, and crime type for each event. We investigate a rich range

of models to enhance our understanding of the set of incidences.

Petros Dellaporta (UCL)

Scalable inference for a full multivariate stochastic volatility model

Abstract: We introduce a multivariate stochastic volatility model for asset returns that imposes no restrictions to the structure of the volatility matrix and treats all its elements as functions of latent stochastic processes. When the number of assets is prohibitively large, we propose a factor multivariate stochastic volatility model in which the variances and correlations of the factors evolve stochastically over time. Inference is achieved via a carefully designed feasible andscalable Markov chain Monte Carlo algorithm that combines two computationally important ingredients: it utilizes invariant to the prior Metropolis proposal densities for simultaneously updating all latent paths and has quadratic, rather than cubic, computational complexity when evaluating the multivariate normal densities required. We apply our modelling and computational methodology to 571 stock daily returns of Euro STOXX index for data over a period of 10 years.

Mikhail Malyutov (Northeastern University)

Context-free and Grammer-free Statistical Testing Identity of Styles

Our theory justifies our thorough statistical modification CCC of D.Khmelev's conditional compression based classification idea of 2001 and the 7 years of intensive applied statistical implementation of CCC for authorship attribution of literary works.

Homogeneity testing based on SCOT training with applications to the financial modeling and Statistical Quality Control are also in progress. Both approaches are desrcibed in a Springer monograph which appears shortly. Stochastic Context Tree (abbreviated as SCOT) is m-Markov Chain with every state of a spring independent of the symbols in its more remote past than the context of length determined by the preceding symbols of this state.

In all of our applications we uncover a complex sparse structure of memory in SCOT models that allows excellent discrimination power. In additiion, a straightforward estimation of the stationary distributio of SCOT gives insight into contexts crucial for discrimination between, say, different regimes of financial data or between styles of different authors of literary tests.

Michael Newton (University of Wisconsin-Madison)

Ranking and selection revisited

In large-scale inference the precision with which individual parameters are estimated may vary greatly among parameters, thus complicating the task to rank order parameters. I present a framework for evaluating different ranking/selection schemes as well as an empirical Bayesian methodology showing theoretical and empirical advantages over available approaches. Examples from genomics and sports will help to illustrate the issues.

Jon Forster (Southampton)

Model integration for mortality estimation and forecasting

The decennial English Life Tables have been produced after every UK decennial census since 1841. They are based on graduated (smoothed) estimates of central mortality rates, or related functions. For UK mortality, over the majority of the age range, a GAM can provide a smooth function which adheres acceptably well to the crude mortality rates. At the very highest ages, the sparsity of the data mean that the uncertainty about mortality rates is much greater. A further issue is that life table estimation requires us to extrapolate the estimate of the mortality rate function to ages beyond the extremes of the observed data. Our approach integrates a GAM at lower ages with a low-dimensional parametric model at higher ages. Uncertainty about the threshold age ,at which the transition to the simpler model occurs, is integrated into the analysis.

This base structure can then be extended into a model for the evolution of mortality rates over time, allowing the forecasting of mortality rates, a key input into demographic projections necessary for planning.

Degui Li (University of York)

Panel Data Models with Interactive Fixed Effects and Multiple Structural Breaks

In this paper we consider estimation of common structural breaks in panel data models with interactive fixed effects which are unobservable. We introduce a penalized principal component (PPC) estimation procedure with an adaptive group fused LASSO to detect the multiple structural breaks in the models. Under some mild conditions, we show that with probability approaching one the proposed method can correctly determine the unknown number of breaks and consistently estimate the common break dates. furthermore, we estimate the regression coefficients through the post-LASSO method and establish the asymptotic distrbution theory for the resulting estimators. The developed methodology and theory are applicable to the case of dynamic panel data models. The Monte Carlo simulation results demonstrate that the proposed method works well in finite samples with low false detection probability when there is no structural break and high probability of correctly estimating the break numbers when the structural breaks exist. We finally apply our method to study the environmental Kuznets curve for 74 countries over 40 years and detect two breaks in the data.

Claire Gormley (University College Dublin)

Clustering High Dimensional Mixed Data: Joint Analysis of Phenotypic and Genotypic Data

The LIPGENE-SU.VI.MAX study, like many others, recorded high dimensional continuous phenotypic data and categorical genotypic data. Interest lies in clustering the study participant into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory.

A novel latent variable model which elegantly accommodates high dimensional, mixed data is developed to cluster participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model.

Two clusters or sub-phenotypes (‘healthy’ and ‘at risk’) are uncovered. A small subset of variables is deemed discriminatory which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, seven years after the data were collected, participants underwent further analysis to diagnose presence or absence of the metabolic syndrome (MetS). The two uncovered sub-phenotypes strongly correspond to the seven year follow up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS, and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition.

Gonzalo Garcia Donato (Universidad Castilla La Mancha)

Criteria for Bayesian model choice

In model choice (or model selection) several statistical models are postulated as legitimate explanations for a response variable and this uncertainty is to be propagated in the inferential process. The type of questions one is aimed to answer is assorted ranging from e.g. identifying the `true’ model to produce more reliable estimates that takes into account this extra source of variability. Particular important problems of model choice are hypothesis testing, model averaging and variable selection. The Bayesian paradigm provides a conceptually simple and unified solution to the model selection problem: the posterior probabilities of the competing models. This is also named the posterior distribution over the model space and is a simple function of Bayes factors. Answering any question of interest just reduces to summarizing properly this posterior distribution.

Unfortunately, the posterior distribution may depend dramatically on the prior inputs and unlike estimation problems (where model is fixed) such sensitivity does not vanish with large sample sizes. Additionally, it is well known that standard solutions like improper or vague priors cannot be used in general as they result in arbitrary Bayes factors. Bayarri et al (2012) propose tackling these difficulties basing the assignment of prior distributions in objective contexts on a number of sensible statistical. This approach takes a step beyond a way of analyzing the problem that Jeffreys inaugurated fifty years ago.

In this talk the criteria will be presented with emphasis on those aspects who serve to characterize features of the priors that, until today, have been popularly used without a clear justification.

Originally the criteria were accompanied with an application to variable selection in regression models and here we will see how they can be useful to tackle other important scenarios like high dimensional settings or survival problems.

Daniel Rudolf - Perturbation theory for Markov chains

Peter Orbanz

Mingli Chen

Satish Iyengar - Big Data Challenges in Psychiatry

 Current psychiatric diagnoses are based primarily on self-reported experiences. Unfortu- nately, treatments for the diagnoses are not effective for all patients. One hypothesized reason is that “artificial grouping of heterogeneous syndromes with different pathophysio- logical mechanisms into one disorder.” To address this problem, the US National Institute of Mental Health instituted the Research Domain Criteria framework in 2009. This re- search framework calls for integrating data from many levels of information: genes, cells, molecules, circuits, physiology, behavior, and self-report. Clustering comes to the forefront as a key tool in this big-data effort. In this talk, we present a case study of the use of mix- ture models to cluster older adults based on measures of sleep from three domains: diary, actigraphy, and polysomnography. Challenges in this effort include the use of mixtures of asymmetric (skewed) distributions, a large number of potential clustering variables, and seeking clinically meaningful solutions. We present novel variable selection algorithms, study them by simulation, and demonstrate our methods on the sleep data. This work is joint with Dr. Meredith Wallace.

Yi Yu (University of Bristol)

Title: Estimating whole brain dynamics using spectral clustering

Abstract: The estimation of time-varying networks for functional Magnetic Resonance Imaging (fMRI) data sets is of increasing importance and interest. In this work, we formulate the problem in a high-dimensional time series framework and introduce a data-driven method, namely Network Change Points Detection (NCPD), which detects change points in the network structure of a multivariate time series, with each component of the time series represented by a node in the network. NCPD is applied to various simulated data and a resting-state fMRI data set. This new methodology also allows us to identify common functional states within and across subjects. Finally, NCPD promises to offer a deep insight into the large-scale characterisations and dynamics of the brain. This is joint work with Ivor Cribben (Alberta School of Business).

Liz Ryan (KCL)

Title: Simulation-based Fully Bayesian Experimental Design

Abstract:

Bayesian experimental design is a fast growing area of research with many real-world applications. As computational power has increased over the years, so has the development of simulation-based design methods, which involve a number of Bayesian algorithms, such as Markov chain Monte Carlo (MCMC) algorithms. However, many of the proposed algorithms have been found to be computationally intensive for complex or nonstandard design problems, such as those which require a large number of design points to be found and/or those for which the observed data likelihood has no analytic expression. In this work, we develop novel extensions of existing algorithms which have been used for Bayesian experimental design, and also incorporate methodologies which have been used for Bayesian inference into the design framework, so that solutions to more complex design problems can be found.

Ioannis Kosmidis

Title:
Reduced-bias inference for regression models with tractable and
intractable likelihoods

Abstract:

This talk focuses on a unified theoretical and algorithmic framework
for reducing bias in the estimation of statistical models from a
practitioners point of view. We will briefly discuss how shortcomings
of classical estimators and of inferential procedures depending on
those can be overcome via reduction of bias, and provide a few
demonstrations stemming from current and past research on well-used
statistical models with tractable likelihoods, including beta
regression for bounded-domain responses, and the typically
small-sample setting of meta-analysis and meta-regression in the
presence of heterogeneity. The large impact that bias in the
estimation of the variance components can have on inference motivates
delivering higher-order corrective methods for generalised linear
mixed models. The challenges in doing that will be presented along
with resolutions stemming from current research.

Marcelo Pereyra

Bayesian inference by convex optimisation: theory, methods, and algorithms.

Abstract:

Convex optimisation has become the main Bayesian computation methodology in many areas of data science such as mathematical imaging and machine learning, where high dimensionality is often addressed by using models that are log-concave and where maximum-a-posteriori (MAP) estimation can be performed efficiently by optimisation. The first part of this talk presents a new decision-theoretic derivation of MAP estimation and shows that, contrary to common belief, under log-concavity MAP estimators are proper Bayesian estimators. A main novelty is that the derivation is based on differential geometry. Following on from this, we establish universal theoretical guarantees for the estimation error involved and show estimation stability in high dimensions. Moreover, the second part of the talk describes a new general methodology for approximating Bayesian high-posterior-density regions in log-concave models. The approximations are derived by using recent concentration of measure results related to information theory, and can be computed very efficiently, even in large-scale problems, by using convex optimisation techniques. The approximations also have favourable theoretical properties, namely they outer-bound the true high-posterior-density credibility regions, and they are stable with respect to model dimension. The proposed methodology is finally illustrated on two high-dimensional imaging inverse problems related to tomographic reconstruction and sparse deconvolution, where they are used to explore the uncertainty about the solutions, and where convex-optimisation-empowered proximal Markov chain Monte Carlo algorithms are used as benchmark to compute exact credible regions and measure the approximation error.

Paul Birrell (MRC Biostatistics Unit, Cambridge)

Towards Computationally Efficient Epidemic Inference

In a pandemic where infection is widespread, there is no direct observation of the infection processes. Instead information comes from a variety of surveillance data schemes that are prone to noise, contamination, bias and sparse sampling. To form an accurate impression of the epidemic and to be able to make forecasts of its evolution, therefore, as many of these data streams as possible need to be assimilated into a single integrated analysis. The result of this is that the transmission model describing the infection process and the linked observation models can become computationally demanding, limiting the capacity for statistical inference in real-time.

I will discuss some of our attempts at making the inferential process more efficient, with particular focus on dynamic emulation, where the computationally expensive epidemic model is replaced by a more readily evaluated proxy, a time-evolving Gaussian process trained on a (relatively) small number of model runs at key input values, training that can be done a priori.

"Adaptive MCMC For Everyone"

Jeffrey Rosenthal, University of Toronto

Markov chain Monte Carlo (MCMC) algorithms, such as the Metropolis
Algorithm and the Gibbs Sampler, are an extremely useful
and popular method of approximately sampling from complicated
probability distributions. Adaptive MCMC attempts to automatically
modify the algorithm while it runs, to improve its performance on
the fly. However, such adaptation often destroys the ergodicity
properties necessary for the algorithm to be valid. In this talk,
we first illustrate MCMC algorithms using simple graphical Java
applets. We then discuss adaptive MCMC, and present examples and
theorems concerning its ergodicity and efficiency. We close with
some recent ideas which make adaptive MCMC more widely applicable
in broader contexts.

Korbinian Strimmer (Imperial)

An entropy approach for integrative genomics and network modeling

Multivariate regression approaches such as Seemingly Unrelated Regression (SUR) or Partial Least Squares (PLS) are commonly used in vertical data integration to jointly analyse different types of omics data measured on the same samples, such as SNP and gene expression data (eQTL) or proteomic and transcriptomic data.  However, these approaches may be difficult to apply and to interpret for computational and conceptual reasons.

Here we present a simple alternative approach to integrative genomics based on using relative entropy to characterise the overall association between two (or more) sets of omic data, and to infer the underlying corresponding association network among the individual covariates.  This approach is computationally inexpensive and can be applied to large-dimensional data sets.  A key and novel feature of our method is decomposition of the total strength between two or more groups of variables based on optimal whitening of the individual data sets.  Correspondingly, it may also be viewed as a special form of a latent-variable multivariate regression model.

We illustrate this approach by analysing metabolomic and transcriptomic data from the DILGOM study.


References:

A. Kessy, A. Lewin, and K. Strimmer. 2017. Optimal whitening and decorrelation. The American Statistician, to appear. http://dx.doi.org/10.1080/00031305.2016.1277159
T. Jendoubi and K. Strimmer. 2017. Data integration and network modeling: an entropy approach.  In prep.

Title: Semi-supervised multiview clustering for high-dimensional data

Abstract: Although the challenges presented by high dimensional data in the context of regression are well-known and the subject of much current research, comparatively little work has been done on this in the context of clustering. In this setting, the key challenge is that often only a small subset of the covariates provides a relevant stratification of the population. Identifying relevant strata can be particularly challenging when dealing with high-dimensional datasets, in which there may be many covariates that provide no information whatsoever about population structure, or – perhaps worse – in which there may be (potentially large) covariate subsets that define irrelevant stratifications. For example, when dealing with genetic data, there may be some genetic variants that allow us to group patients in terms of disease risk, but others that would provide completely irrelevant stratifications (e.g. which would group patients together on the basis of eye or hair colour). Bayesian profile regression is a semi-supervised model-based clustering approach that makes use of a response in order to guide the clustering toward relevant stratifications. Here we consider how this approach can be extended to the "multiview" setting, in which different groups of covariates ("views") define different stratifications. We also present a heuristic alternative, some preliminary results in the context of breast cancer subtyping, and consider how the approach could also be used to integrate different 'omics datasets (assuming that each dataset provides measurements on a common set of individuals).

Speaker: Davide Pigoli (King's College London)

Title: Functional data analysis of biological growth processes

 Abstract: Functional data are examples of high-dimensional data when the observed variables have a natural ordering and are generated by an underlying smooth process. These additional properties allow us to develop methods that go beyond what would be possible with classical multivariate techniques. In this talk, I will demonstrate the potential of functional data analysis for biological growth processes in two different applications. The first one is in forensic entomology, where there is the need of estimating time-dependent growth curves from experiments where larvae have been exposed to a relatively small number of constant temperature profiles. The second one is in quantitative genetics, where the growth curve is a function-valued phenotypic trait from which the continuous genetic variation needs to be estimated.

Speaker: Jonathan Keith (Monash University)

Title: Markov chain Monte Carlo in discrete spaces, with applications in bioinformatics and ecology

 Abstract: Efficient sampling of probability distributions over large discrete spaces is a challenging problem that arises in many contexts in bioinformatics and ecology. For example, segmentation of genomes to identify putative functional elements can be cast as a multiple change-point problem involving thousands or even millions of change-points. Another example involves reconstructing the invasion history of an introduced species by embedding a phylogenetic tree in a landscape. A third example involves inferring networks of molecular interactions in cellular systems.

 In this talk I describe a generalisation of the Gibbs sampler that allows this well known strategy for sampling probability distributions in R^n to be adapted for sampling discrete spaces. The technique has been successfully applied to each of the problems mentioned above. However, these problems remain highly computationally intensive. I will discuss a number of alternatives for efficient sampling of such spaces, and will be seeking collaborations to develop these and other new approaches.

3-4pm A1.01, Nov 24, 2017 - Song Liu

Title: Trimmed Density Ratio Estimation

Abstract: Density ratio estimation has become a versatile tool in machine learning community recently. However, due to its unbounded nature, density ratio estimation is vulnerable to corrupted data points, which often pushes the estimated ratio toward infinity. In this paper, we present a robust estimator which automatically identifies and trims outliers. The proposed estimator has a convex formulation, and the global optimum can be obtained via subgradient descent. We analyze the parameter estimation error of this estimator under high-dimensional settings. Experiments are conducted to verify the effectiveness of the estimator.