Paul Burton

Base 'DataSHIELD' functions for the client side. 'DataSHIELD' is a software package which allows you to do non-disclosive federated analysis on sensitive data. 'DataSHIELD' analytic functions have been designed to only share non disclosive summary statistics, with built in automated output checking based on statistical disclosure control. With data sites setting the threshold values for the automated output checks. For more details, see citation('dsBaseClient').

Base 'DataSHIELD' functions for the server side. 'DataSHIELD' is a software package which allows you to do non-disclosive federated analysis on sensitive data. 'DataSHIELD' analytic functions have been designed to only share non disclosive summary statistics, with built in automated output checking based on statistical disclosure control. With data sites setting the threshold values for the automated output checks. For more details, see 'citation("dsBase")'.

Motivation: The validity of epidemiologic findings can be increased using triangulation, i.e. comparison of findings across contexts, and by having sufficiently large amounts of relevant data to analyse. However, access to data is often constrained by practical considerations and by ethico-legal and data governance restrictions. Gaining access to such data can be time-consuming due to the governance requirements associated with data access requests to institutions in different jurisdictions. Results: DataSHIELD is a software solution that enables remote analysis without the need for data transfer (federated analysis). DataSHIELD is a scientifically mature, open-source data access and analysis platform aligned with the ‘Five Safes’ framework, the international framework governing safe research access to data. It allows real-time analysis while mitigating disclosure risk through an active multi-layer system of disclosure-preventing mechanisms. This combination of real-time remote statistical analysis, disclosure prevention mechanisms, and federation capabilities makes DataSHIELD a solution for addressing many of the technical and regulatory challenges in performing the large-scale statistical analysis of health and biomedical data. This paper describes the key components that comprise the disclosure protection system of DataSHIELD. These broadly fall into three classes: (i) system protection elements, (ii) analysis protection elements, and (iii) governance protection elements. Availability and implementation: Information about the DataSHIELD software is available in https://datashield.org/ and https://github.com/datashield.

Background: Preterm birth is the leading cause of perinatal morbidity and mortality and is associated with adverse developmental and long-term health outcomes, including several cardiometabolic risk factors and outcomes. However, evidence about the association of preterm birth with later body size derives mainly from studies using birth weight as a proxy of prematurity rather than an actual length of gestation. We investigated the association of gestational age (GA) at birth with body size from infancy through adolescence. Methods and findings: We conducted a two-stage individual participant data (IPD) meta-analysis using data from 253,810 mother–child dyads from 16 general population-based cohort studies in Europe (Denmark, Finland, France, Italy, Norway, Portugal, Spain, the Netherlands, United Kingdom), North America (Canada), and Australasia (Australia) to estimate the association of GA with body mass index (BMI) and overweight (including obesity) adjusted for the following maternal characteristics as potential confounders: education, height, prepregnancy BMI, ethnic background, parity, smoking during pregnancy, age at child’s birth, gestational diabetes and hypertension, and preeclampsia. Pregnancy and birth cohort studies from the LifeCycle and the EUCAN-Connect projects were invited and were eligible for inclusion if they had information on GA and minimum one measurement of BMI between infancy and adolescence. Using a federated analytical tool (DataSHIELD), we fitted linear and logistic regression models in each cohort separately with a complete-case approach and combined the regression estimates and standard errors through random-effects study-level meta-analysis providing an overall effect estimate at early infancy (>0.0 to 0.5 years), late infancy (>0.5 to 2.0 years), early childhood (>2.0 to 5.0 years), mid-childhood (>5.0 to 9.0 years), late childhood (>9.0 to 14.0 years), and adolescence (>14.0 to 19.0 years). GA was positively associated with BMI in the first decade of life, with the greatest increase in mean BMI z-score during early infancy (0.02, 95% confidence interval (CI): 0.00; 0.05, p < 0.05) per week of increase in GA, while in adolescence, preterm individuals reached similar levels of BMI (0.00, 95% CI: −0.01; 0.01, p 0.9) as term counterparts. The association between GA and overweight revealed a similar pattern of association with an increase in odds ratio (OR) of overweight from late infancy through mid-childhood (OR 1.01 to 1.02) per week increase in GA. By adolescence, however, GA was slightly negatively associated with the risk of overweight (OR 0.98 [95% CI: 0.97; 1.00], p 0.1) per week of increase in GA. Although based on only four cohorts (n = 32,089) that reached the age of adolescence, data suggest that individuals born very preterm may be at increased odds of overweight (OR 1.46 [95% CI: 1.03; 2.08], p < 0.05) compared with term counterparts. Findings were consistent across cohorts and sensitivity analyses despite considerable heterogeneity in cohort characteristics. However, residual confounding may be a limitation in this study, while findings may be less generalisable to settings in low- and middle-income countries. Conclusions: This study based on data from infancy through adolescence from 16 cohort studies found that GA may be important for body size in infancy, but the strength of association attenuates consistently with age. By adolescence, preterm individuals have on average a similar mean BMI to peers born at term.

Motivation: DataSHIELD is an open-source software infrastructure enabling the analysis of data distributed across multiple databases (federated data) without leaking individuals’ information (non-disclosive). It has applications in many scientific domains, ranging from biosciences to social sciences and including high-throughput genomic studies. R is the language used to interact with (and build) DataSHIELD. This creates difficulties for researchers who do not have experience writing R code or lack the time to learn how to use the DataSHIELD functions. To help new researchers use the DataSHIELD infrastructure and to improve the user-friendliness for experienced researchers, we present ShinyDataSHIELD. Implementation: ShinyDataSHIELD is a web application with an R backend that serves as a graphical user interface (GUI) to the DataSHIELD infrastructure. General features: The version of the application presented here includes modules to perform: (i) exploratory analysis through descriptive summary statistics and graphical representations (scatter plots, histograms, heatmaps and boxplots); (ii) statistical modelling (generalized linear fixed and mixed-effects models, survival analysis through Cox regression); (iii) genome-wide association studies (GWAS); and (iv) omic analysis (transcriptomics, epigenomics and multi-omic integration). Availability: ShinyDataSHIELD is publicly hosted online [https://datashield-demo.obiba.org/], the source code and user guide are deposited on Zenodo DOI 10.5281/zenodo.6500323, freely available to non-commercial users under ‘Commons Clause’ License Condition v1.0. Docker images are also available [https://hub.docker.com/r/brgelab/shiny-data-shield].

In multi-cohort machine learning studies, it is critical to differentiate between effects that are reproducible across cohorts and those that are cohort-specific. Multi-task learning (MTL) is a machine learning approach that facilitates this differentiation through the simultaneous learning of prediction tasks across cohorts. Since multi-cohort data can often not be combined into a single storage solution, there would be the substantial utility of an MTL application for geographically distributed data sources. Here, we describe the development of ‘dsMTL’, a computational framework for privacy-preserving, distributed multi-task machine learning that includes three supervised and one unsupervised algorithms. First, we derive the theoretical properties of these methods and the relevant machine learning workflows to ensure the validity of the software implementation. Second, we implement dsMTL as a library for the R programming language, building on the DataSHIELD platform that supports the federated analysis of sensitive individual-level data. Third, we demonstrate the applicability of dsMTL for comorbidity modeling in distributed data. We show that comorbidity modeling using dsMTL outperformed conventional, federated machine learning, as well as the aggregation of multiple models built on the distributed datasets individually. The application of dsMTL was computationally efficient and highly scalable when applied to moderate-size (n < 500), real expression data given the actual network latency. dsMTL is freely available at https://github.com/transbioZI/dsMTLBase (server-side package) and https://github.com/transbioZI/dsMTLClient (client-side package). Supplementary data are available at Bioinformatics online.

Combined analysis of multiple, large datasets is a common objective in the health- and biosciences. Existing methods tend to require researchers to physically bring data together in one place or follow an analysis plan and share results. Developed over the last 10 years, the DataSHIELD platform is a collection of R packages that reduce the challenges of these methods. These include ethico-legal constraints which limit researchers’ ability to physically bring data together and the analytical inflexibility associated with conventional approaches to sharing results. The key feature of DataSHIELD is that data from research studies stay on a server at each of the institutions that are responsible for the data. Each institution has control over who can access their data. The platform allows an analyst to pass commands to each server and the analyst receives results that do not disclose the individual-level data of any study participants. DataSHIELD uses Opal which is a data integration system used by epidemiological studies and developed by the OBiBa open source project in the domain of bioinformatics. However, until now the analysis of big data with DataSHIELD has been limited by the storage formats available in Opal and the analysis capabilities available in the DataSHIELD R packages. We present a new architecture (“resources”) for DataSHIELD and Opal to allow large, complex datasets to be used at their original location, in their original format and with external computing facilities. We provide some real big data analysis examples in genomics and geospatial projects. For genomic data analyses, we also illustrate how to extend the resources concept to address specific big data infrastructures such as GA4GH or EGA, and make use of shell commands. Our new infrastructure will help researchers to perform data analyses in a privacy-protected way from existing data sharing initiatives or projects. To help researchers use this framework, we describe selected packages and present an online book (https://isglobal-brge.github.io/resource_bookdown).

We aimed to determine the effects of laparoscopic adjustable gastric band (LAGB) on beta-cell function in overweight people with type 2 diabetes and to assess the relationship between baseline beta-cell function and glycemic outcomes. We studied 44 overweight but not obese people with type 2 diabetes who participated in a randomized trial whose primary outcome was the rate of diabetes remission after 2 years of multidisciplinary diabetes care (MDC group) or multidisciplinary care combined with LAGB. Dynamic beta-cell function was assessed by intravenous glucose challenge, and basal beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) were determined using the homeostatic model. Twelve LAGB participants and two MDC participants were in diabetes remission at 2 years. HOMA-S and the C-peptide response to intravenous glucose increased significantly in LAGB but not in MDC participants. The insulin response to glucose did not change in LAGB participants, whereas their fasting C-peptide/insulin ratio increased. Baseline measures of beta-cell function correlated with diabetes remission but not with reduction in HbA1c following LAGB. In overweight people with diabetes, LAGB improves endogenous beta-cell function after 2 years. Baseline beta-cell function correlated with diabetes remission, but not with HbA1c change following LAGB.

Summary. To investigate the survival of infants with neural tube defects in Western Australia from 1966 to 1990, cases of neural tube defects were ascertained from multiple sources. Survival of infants with anencephaly, spina bifida, and encephalocoele was examined separately, and four birth cohorts were compared: 1966–1972 (when most surviving infants were actively treated), 1973–1979 (a period of stringent application of selection criteria for treatment), 1980–1985 (some relaxation of selection criteria), and 1986–1990 (further relaxation of selection criteria).There was an increase in terminations of pregnancies affected with anencephaly over the study period, and a fall in the proportion of both liveborn and stillborn infants with anencephaly. Most liveborn infants (76.4%) died in the first 24 hours, and none survived longer than 5 days. Most infants with encephalocoele (76.4%) were liveborn, and survival was poorest in the 1973–1979 cohort, although the difference in survival across cohorts just failed to attain a formal level of significance. For spina bifida, there was an increase in terminations of affected pregnancies over the study period. Survival of liveborn infants with spina bifida was poorest in the 1973–1979 cohort, and greatest in the most recent cohort. These improvements in survival are likely to be the result of relaxation of selection criteria for treatment, improvements in treatment and, to a lesser extent, selective termination of affected pregnancies.