OBJECTIVE: This study aims to address the gap in the literature on converting real-world Clinical Document Architecture (CDA) data into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM), focusing on the initial steps preceding the mapping phase. We highlight the importance of a repeatable Extract-Transform-Load (ETL) pipeline for health data extraction from HL7 CDA documents in Estonia for research purposes. METHODS: We developed a repeatable ETL pipeline to facilitate the extraction, cleaning, and restructuring of health data from CDA documents to OMOP CDM, ensuring a high-quality and structured data format. This pipeline was designed to adapt to continuously updated data exchange format changes and handle various CDA document subsets for different scientific studies. RESULTS: We demonstrated via selected use cases that our pipeline successfully transformed a significant portion of diagnosis codes, body weight and eGFR measurements, and PAP test results from CDA documents into OMOP CDM, showing the ease of extracting structured data. However, challenges such as harmonising diverse coding systems and extracting lab results from free-text sections were encountered. The iterative development of the pipeline facilitated swift error detection and correction, enhancing the process's efficiency. CONCLUSION: After a decade of focused work, our research has led to the development of an ETL pipeline that effectively transforms HL7 CDA documents into OMOP CDM in Estonia, addressing key data extraction and transformation challenges. The pipeline's repeatability and adaptability to various data subsets make it a valuable resource for researchers dealing with health data. While tested on Estonian data, the principles outlined are broadly applicable, potentially aiding in handling health data standards that vary by country. Despite newer health data standards emerging, the relevance of CDA for retrospective health studies ensures the continuing importance of this work.

The goal of the EstNLTK Python library is to provide a unified programming interface for natural language processing in Estonian. As such, previous versions of the library have been immensely successful both in academic and industrial circles. However, they also contained serious structural limitations – it was hard to add new components and there was a lack of fine-grained control needed for back-end programming. These issues have been explicitly addressed in the EstNLTK library while preserving the intuitive interface for novices. We have remastered the basic NLP pipeline by adding many data cleaning steps that are necessary for analyzing real-life texts, and state of the art components for morphological analysis and fact extraction. Our evaluation on unlabelled data shows that the remastered basic NLP pipeline outperforms both the previous version of the toolkit, as well as neural models of StanfordNLP. In addition, EstNLTK contains a new interface for storing, processing and querying text objects in Postgres database which greatly simplifies processing of large text collections. EstNLTK is freely available under the GNU GPL version 2 license, which is standard for academic software.

We improve the quality of cryptographically privacy-preserving genome-wide association studies by correctly handling population stratification-the inherent genetic difference of patient groups, e.g., people with different ancestries. Our approach is to use principal component analysis to reduce the dimensionality of the problem so that we get less spurious correlations between traits of interest and certain positions in the genome. While this approach is commonplace in practical genomic analysis, it has not been used within a privacy-preserving setting. In this paper, we use cryptographically secure multi-party computation to tackle principal component analysis, and present an implementation and experimental results showing the performance of the approach.

Secure multi-party computation is a practical cryptographic method for processing confidential data. Research progress has led to its use in privacy-preserving statistical analysis. Implementations of simple statistical analysis functions have been published, but no comprehensive tool has been built. We describe and implement a suite of most used statistical analysis functions in the privacy-preserving setting including simple statistics, t-test, chi-squared test, Wilcoxon tests and linear regression. We give descriptions of the privacy-preserving algorithms and benchmark results that show an order of magnitude improvement over previous work.

MOTIVATION: One of the main goals of large scale methylation studies is to detect differentially methylated loci. One way is to approach this problem sitewise, i.e. to find differentially methylated positions (DMPs). However, it has been shown that methylation is regulated in longer genomic regions. So it is more desirable to identify differentially methylated regions (DMRs) instead of DMPs. The new high coverage arrays, like Illuminas 450k platform, make it possible at a reasonable cost. Few tools exist for DMR identification from this type of data, but there is no standard approach. RESULTS: We propose a novel method for DMR identification that detects the region boundaries according to the minimum description length (MDL) principle, essentially solving the problem of model selection. The significance of the regions is established using linear mixed models. Using both simulated and large publicly available methylation datasets, we compare seqlm performance to alternative approaches. We demonstrate that it is both more sensitive and specific than competing methods. This is achieved with minimal parameter tuning and, surprisingly, quickest running time of all the tried methods. Finally, we show that the regional differential methylation patterns identified on sparse array data are confirmed by higher resolution sequencing approaches. AVAILABILITY AND IMPLEMENTATION: The methods have been implemented in R package seqlm that is available through Github: https://github.com/raivokolde/seqlm CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Secure multi-party computation systems are commonly built from a small set of primitive components. The compos ability of security notions has a central role in the analysis of such systems, as it allows us to deduce security properties of complex protocols from the properties of its components. We show that the standard notions of universally compos able security are overly restrictive in this context and can lead to protocols with sub-optimal performance. As a remedy, we introduce a weaker notion of privacy that is satisfied by simpler protocols and is preserved by composition. After that we fix a passive security model and show how to convert a private protocol into a universally compos able protocol. As a result, we obtain modular security proofs without performance penalties.

MOTIVATION: Increased availability of various genotyping techniques has initiated a race for finding genetic markers that can be used in diagnostics and personalized medicine. Although many genetic risk factors are known, key causes of common diseases with complex heritage patterns are still unknown. Identification of such complex traits requires a targeted study over a large collection of data. Ideally, such studies bring together data from many biobanks. However, data aggregation on such a large scale raises many privacy issues. RESULTS: We show how to conduct such studies without violating privacy of individual donors and without leaking the data to third parties. The presented solution has provable security guarantees. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: The continued progress in developing technological platforms, availability of many published experimental datasets, as well as different statistical methods to analyze those data have allowed approaching the same research question using various methods simultaneously. To get the best out of all these alternatives, we need to integrate their results in an unbiased manner. Prioritized gene lists are a common result presentation method in genomic data analysis applications. Thus, the rank aggregation methods can become a useful and general solution for the integration task. RESULTS: Standard rank aggregation methods are often ill-suited for biological settings where the gene lists are inherently noisy. As a remedy, we propose a novel robust rank aggregation (RRA) method. Our method detects genes that are ranked consistently better than expected under null hypothesis of uncorrelated inputs and assigns a significance score for each gene. The underlying probabilistic model makes the algorithm parameter free and robust to outliers, noise and errors. Significance scores also provide a rigorous way to keep only the statistically relevant genes in the final list. These properties make our approach robust and compelling for many settings. AVAILABILITY: All the methods are implemented as a GNU R package RobustRankAggreg, freely available at the Comprehensive R Archive Network http://cran.r-project.org/.

We propose private protocols implementing the Kernel Adatron and Kernel Perceptron learning algorithms, give private classification protocols and private polynomial kernel computation protocols. The new protocols return their outputs - either the kernel value, the classifier or the classifications - in encrypted form so that they can be decrypted only by a common agreement by the protocol participants. We show how to use the encrypted classifications to privately estimate many properties of the data and the classifier. The new SVM classifiers are the first to be proven private according to the standard cryptographic definitions.