An important component of every country's COVID-19 response is fast and efficient testing -- to identify and isolate cases, as well as for early detection of local hotspots. For many countries, producing a sufficient number of tests has been a serious limiting factor in their efforts to control COVID-19 infections. Group testing is a well-established mathematical tool, which can provide a serious and rapid improvement to this situation. In this note, we compare several well-established group testing schemes in the context of qPCR testing for COVID-19. We include example calculations, where we indicate which testing architectures yield the greatest efficiency gains in various settings. We find that for identification of individuals with COVID-19, array testing is usually the best choice, while for estimation of COVID-19 prevalence rates in the total population, Gibbs-Gower testing usually provides the most accurate estimates given a fixed and relatively small number of tests. This note is intended as a helpful handbook for labs implementing group testing methods.

Effective property prediction methods can help accelerate the search for COVID-19 antivirals either through accurate in-silico screens or by effectively guiding on-going at-scale experimental efforts. However, existing prediction tools have limited ability to accommodate scarce or fragmented training data currently available. In this paper, we introduce a novel approach to learn predictors that can generalize or extrapolate beyond the heterogeneous data. Our method builds on and extends recently proposed invariant risk minimization, adaptively forcing the predictor to avoid nuisance variation. We achieve this by continually exercising and manipulating latent representations of molecules to highlight undesirable variation to the predictor. To test the method we use a combination of three data sources: SARS-CoV-2 antiviral screening data, molecular fragments that bind to SARS-CoV-2 main protease and large screening data for SARS-CoV-1. Our predictor outperforms state-of-the-art transfer learning methods by significant margin. We also report the top 20 predictions of our model on Broad drug repurposing hub.

We present the R package mgm for the estimation of k-order mixed graphical models (MGMs) and mixed vector autoregressive (mVAR) models in high-dimensional data. These are a useful extensions of graphical models for only one variable type, since data sets consisting of mixed types of variables (continuous, count, categorical) are ubiquitous. In addition, we allow to relax the stationarity assumption of both models by introducing time-varying versions of MGMs and mVAR models based on a kernel weighting approach. Time-varying models offer a rich description of temporally evolving systems and allow to identify external influences on the model structure such as the impact of interventions. We provide the background of all implemented methods and provide fully reproducible examples that illustrate how to use the package.

Sparse estimation via penalized likelihood (PL) is now a popular approach to learn the associations among a large set of variables. This paper describes an R package called lslx that implements PL methods for semi-confirmatory structural equation modeling (SEM). In this semi-confirmatory approach, each model parameter can be specified as free/fixed for theory testing, or penalized for exploration. By incorporating either a L1 or minimax concave penalty, the sparsity pattern of the parameter matrix can be efficiently explored. Package lslx minimizes the PL criterion through a quasi-Newton method. The algorithm conducts line search and checks the first-order condition in each iteration to ensure the optimality of the obtained solution. A numerical comparison between competing packages shows that lslx can reliably find PL estimates with the least time. The current package also supports other advanced functionalities, including a two-stage method with auxiliary variables for missing data handling and a reparameterized multi-group SEM to explore population heterogeneity.

The random-effects or normal-normal hierarchical model is commonly utilized in a wide range of meta-analysis applications. A Bayesian approach to inference is very attractive in this context, especially when a meta-analysis is based only on few studies. The bayesmeta R package provides readily accessible tools to perform Bayesian meta-analyses and generate plots and summaries, without having to worry about computational details. It allows for flexible prior specification and instant access to the resulting posterior distributions, including prediction and shrinkage estimation, and facilitating for example quick sensitivity checks. The present paper introduces the underlying theory and showcases its usage.

This paper introduces the funData R package as an object-oriented implementation of functional data. It implements a unified framework for dense univariate and multivariate functional data on one- and higher dimensional domains as well as for irregular functional data. The aim of this package is to provide a user-friendly, self-contained core toolbox for functional data, including important functionalities for creating, accessing and modifying functional data objects, that can serve as a basis for other packages. The package further contains a full simulation toolbox, which is a useful feature when implementing and testing new methodological developments. Based on the theory of object-oriented data analysis, it is shown why it is natural to implement functional data in an object-oriented manner. The classes and methods provided by funData are illustrated in many examples using two freely available datasets. The MFPCA package, which implements multivariate functional principal component analysis, is presented as an example for an advanced methodological package that uses the funData package as a basis, including a case study with real data. Both packages are publicly available on GitHub and the Comprehensive R Archive Network.

The R package mvord implements composite likelihood estimation in the class of multivariate ordinal regression models with a multivariate probit and a multivariate logit link. A flexible modeling framework for multiple ordinal measurements on the same subject is set up, which takes into consideration the dependence among the multiple observations by employing different error structures. Heterogeneity in the error structure across the subjects can be accounted for by the package, which allows for covariate dependent error structures. In addition, different regression coefficients and threshold parameters for each response are supported. If a reduction of the parameter space is desired, constraints on the threshold as well as on the regression coefficients can be specified by the user. The proposed multivariate framework is illustrated by means of a credit risk application.

An R package for computing the all-subsets regression problem is presented. The proposed algorithms are based on computational strategies recently developed. A novel algorithm for the best-subset regression problem selects subset models based on a predetermined criterion. The package user can choose from exact and from approximation algorithms. The core of the package is written in C++ and provides an efficient implementation of all the underlying numerical computations. A case study and benchmark results illustrate the usage and the computational efficiency of the package.

This paper is devoted to the R package JSM which performs joint statistical modeling of survival and longitudinal data. In biomedical studies it has been increasingly common to collect both baseline and longitudinal covariates along with a possibly censored survival time. Instead of analyzing the survival and longitudinal outcomes separately, joint modeling approaches have attracted substantive attention in the recent literature and have been shown to correct biases from separate modeling approaches and enhance information. Most existing approaches adopt a linear mixed effects model for the longitudinal component and the Cox proportional hazards model for the survival component. We extend the Cox model to a more general class of transformation models for the survival process, where the baseline hazard function is completely unspecified leading to semiparametric survival models. We also offer a non-parametric multiplicative random effects model for the longitudinal process in JSM in addition to the linear mixed effects model. In this paper, we present the joint modeling framework that is implemented in JSM, as well as the standard error estimation methods, and illustrate the package with two real data examples: a liver cirrhosis data and a Mayo Clinic primary biliary cirrhosis data.

Manifold optimization appears in a wide variety of computational problems in the applied sciences. In recent statistical methodologies such as sufficient dimension reduction and regression envelopes, estimation relies on the optimization of likelihood functions over spaces of matrices such as the Stiefel or Grassmann manifolds. Recently, Huang, Absil, Gallivan, and Hand (2016) have introduced the library ROPTLIB, which provides a framework and state of the art algorithms to optimize real-valued objective functions over commonly used matrix-valued Riemannian manifolds. This article presents ManifoldOptim, an R package that wraps the C++ library ROPTLIB. ManifoldOptim enables users to access functionality in ROPTLIB through R so that optimization problems can easily be constructed, solved, and integrated into larger R codes. Computationally intensive problems can be programmed with Rcpp and RcppArmadillo, and otherwise accessed through R. We illustrate the practical use of ManifoldOptim through several motivating examples involving dimension reduction and envelope methods in regression.

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 7 November. Speaker: Dr Michael Brown (University of Roehampton), ‘Anxiety and compassion: emotions and the surgical encounter in early 19th-century Britain’ The historical study of the… Continue reading

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 21 November. Speaker: Professor Roberta Gilchrist (University of Reading), ‘The archaeology of monastic healing: spirit, mind and body’ This paper highlights the potential of archaeology to… Continue reading

The History of Pre-Modern Medicine seminar series returns this month. The 2017–18 series – organised by a group of historians of medicine based at London universities and hosted by the Wellcome Library – will conclude with four seminars. The series… Continue reading

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 16 January. Speaker: Dr Catherine Rider (University of Exeter) Medieval Ideas about Infertility and Old Age Abstract: When they discussed fertility and reproductive disorders it was common… Continue reading

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 30 January. Speaker: Professor Guido Alfani (Bocconi University, Milan) Plague in Italy and Europe during the 17th century: epidemiology and impact Abstract: After many years of relative… Continue reading

Broadcasting Health and Disease: Bodies, markets and television, 1950s–1980s An ERC BodyCapital international conference to be held at the Wellcome Trust, 19–21 February 2018 In the television age, health and the body have been broadcasted in many ways: in short… Continue reading

The next seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 13 February. Speaker: Dr William Tullett (Institute of Historical Research, University of London) Smell and medical efficacy in 18th-century England Abstract: In recent years a growing scholarship… Continue reading

The last seminar in the 2017–18 History of Pre-Modern Medicine seminar series takes place on Tuesday 27 February. Speaker: Dr Dror Weil (Max Planck Institute for the History of Science, Berlin) Bodies translated: the circulation of Arabo-Persian physiological theories in late… Continue reading

A free manuscripts workshop for PhD students at Wellcome Collection, 01 June 2018 Engaging with an artefact from the past is often a powerful experience, eliciting emotional and sensory, as well as analytical, responses. Researchers in the library at Wellcome… Continue reading

It’s goodbye from the Wellcome Library blog. The blog is closing and will no longer be updated. Thank you to those that have read the blog, shared it and posted comments. I hope all our readers have enjoyed being able… Continue reading