BACKGROUND: Digital transformation, particularly the integration of medical imaging with clinical data, is vital in personalized medicine. The Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) standardizes health data. However, integrating medical imaging remains a challenge.
OBJECTIVE: This study proposes a method for combining medical imaging data with the OMOP CDM to improve multimodal research.
METHODS: Our approach included the analysis and selection of digital imaging and communications in medicine header tags, validation of data formats, and alignment according to the OMOP CDM framework. The Fast Healthcare Interoperability Resources ImagingStudy profile guided our consistency in column naming and definitions. Imaging Common Data Model (I-CDM), constructed using the entity-attribute-value model, facilitates scalable and efficient medical imaging data management. For patients with lung cancer diagnosed between 2010 and 2017, we introduced 4 new tables-IMAGING_STUDY, IMAGING_SERIES, IMAGING_ANNOTATION, and FILEPATH-to standardize various imaging-related data and link to clinical data.
RESULTS: This framework underscores the effectiveness of I-CDM in enhancing our understanding of lung cancer diagnostics and treatment strategies. The implementation of the I-CDM tables enabled the structured organization of a comprehensive data set, including 282,098 IMAGING_STUDY, 5,674,425 IMAGING_SERIES, and 48,536 IMAGING_ANNOTATION records, illustrating the extensive scope and depth of the approach. A scenario-based analysis using actual data from patients with lung cancer underscored the feasibility of our approach. A data quality check applying 44 specific rules confirmed the high integrity of the constructed data set, with all checks successfully passed, underscoring the reliability of our findings.
CONCLUSIONS: These findings indicate that I-CDM can improve the integration and analysis of medical imaging and clinical data. By addressing the challenges in data standardization and management, our approach contributes toward enhancing diagnostics and treatment strategies. Future research should expand the application of I-CDM to diverse disease populations and explore its wide-ranging utility for medical conditions.

In recent years several experimental observations demonstrated that the gut microbiome plays a role in regulating positively or negatively metabolic homeostasis. Indole-3-propionic acid (IPA), a Tryptophan catabolic product mainly produced by C. Sporogenes, has been recently shown to exert either favorable or unfavorable effects in the context of metabolic and cardiovascular diseases. We performed a study to delineate clinical and multiomics characteristics of human subjects characterized by low and high IPA levels. Subjects with low IPA blood levels showed insulin resistance, overweight, low-grade inflammation, and features of metabolic syndrome compared to those with high IPA. Metabolomics analysis revealed that IPA was negatively correlated with leucine, isoleucine, and valine metabolism. Transcriptomics analysis in colon tissue revealed the enrichment of several signaling, regulatory, and metabolic processes. Metagenomics revealed several OTU of ruminococcus, alistipes, blautia, butyrivibrio and akkermansia were significantly enriched in highIPA group while in lowIPA group Escherichia-Shigella, megasphera, and Desulfovibrio genus were more abundant. Next, we tested the hypothesis that treatment with IPA in a mouse model may recapitulate the observations of human subjects, at least in part. We found that a short treatment with IPA (4 days at 20/mg/kg) improved glucose tolerance and Akt phosphorylation in the skeletal muscle level, while regulating blood BCAA levels and gene expression in colon tissue, all consistent with results observed in human subjects stratified for IPA levels. Our results suggest that treatment with IPA may be considered a potential strategy to improve insulin resistance in subjects with dysbiosis.

Due to the heterogeneity of the randomized controlled trial (RCT) and external target populations, the estimated treatment effect from the RCT is not directly applicable to the target population. For example, the patient characteristics of the ACTG 175 HIV trial are significantly different from that of the three external target populations of interest: US early-stage HIV patients, Thailand HIV patients, and southern Ethiopia HIV patients. This paper considers several methods to transport the treatment effect from the ACTG 175 HIV trial to the target populations beyond the trial population. Most transport methods focus on continuous and binary outcomes; on the contrary, we derive and discuss several transport methods for survival outcomes: an outcome regression method based on a Cox proportional hazard (PH) model, an inverse probability weighting method based on the models for treatment assignment, sampling score, and censoring, and a doubly robust method that combines both methods, called the augmented calibration weighting (ACW) method. However, as the PH assumption was found to be incorrect for the ACTG 175 trial, the methods that depend on the PH assumption may lead to the biased quantification of the treatment effect. To account for the violation of the PH assumption, we extend the ACW method with the linear spline-based hazard regression model that does not require the PH assumption. Applying the aforementioned methods for transportability, we explore the effect of PH assumption, or the violation thereof, on transporting the survival results from the ACTG 175 trial to various external populations.

BACKGROUND: In Multiple Sclerosis (MS), patients´ characteristics and (bio)markers that reliably predict the individual disease prognosis at disease onset are lacking. Cohort studies allow a close follow-up of MS histories and a thorough phenotyping of patients. Therefore, a multicenter cohort study was initiated to implement a wide spectrum of data and (bio)markers in newly diagnosed patients.
METHODS: ProVal-MS (Prospective study to validate a multidimensional decision score that predicts treatment outcome at 24 months in untreated patients with clinically isolated syndrome or early Relapsing-Remitting-MS) is a prospective cohort study in patients with clinically isolated syndrome (CIS) or Relapsing-Remitting (RR)-MS (McDonald 2017 criteria), diagnosed within the last two years, conducted at five academic centers in Southern Germany. The collection of clinical, laboratory, imaging, and paraclinical data as well as biosamples is harmonized across centers. The primary goal is to validate (discrimination and calibration) the previously published DIFUTURE MS-Treatment Decision score (MS-TDS). The score supports clinical decision-making regarding the options of early (within 6 months after study baseline) platform medication (Interferon beta, glatiramer acetate, dimethyl/diroximel fumarate, teriflunomide), or no immediate treatment (> 6 months after baseline) of patients with early RR-MS and CIS by predicting the probability of new or enlarging lesions in cerebral magnetic resonance images (MRIs) between 6 and 24 months. Further objectives are refining the MS-TDS score and providing data to identify new markers reflecting disease course and severity. The project also provides a technical evaluation of the ProVal-MS cohort within the IT-infrastructure of the DIFUTURE consortium (Data Integration for Future Medicine) and assesses the efficacy of the data sharing techniques developed.
CONCLUSIONS: Clinical cohorts provide the infrastructure to discover and to validate relevant disease-specific findings. A successful validation of the MS-TDS will add a new clinical decision tool to the armamentarium of practicing MS neurologists from which newly diagnosed MS patients may take advantage. Trial registration ProVal-MS has been registered in the German Clinical Trials Register, `Deutsches Register Klinischer Studien` (DRKS)-ID: DRKS00014034, date of registration: 21 December 2018; https://drks.de/search/en/trial/DRKS00014034.

Accurate identification of cell cycle phases in single-cell RNA-sequencing (scRNA-seq) data is crucial for biomedical research. Many methods have been developed to tackle this challenge, employing diverse approaches to predict cell cycle phases. In this review article, we delve into the standard processes in identifying cell cycle phases within scRNA-seq data and present several representative methods for comparison. To rigorously assess the accuracy of these methods, we propose an error function and employ multiple benchmarking datasets encompassing human and mouse data. Our evaluation results reveal a key finding: the fit between the reference data and the dataset being analyzed profoundly impacts the effectiveness of cell cycle phase identification methods. Therefore, researchers must carefully consider the compatibility between the reference data and their dataset to achieve optimal results. Furthermore, we explore the potential benefits of incorporating benchmarking data with multiple known cell cycle phases into the analysis. Merging such data with the target dataset shows promise in enhancing prediction accuracy. By shedding light on the accuracy and performance of cell cycle phase prediction methods across diverse datasets, this review aims to motivate and guide future methodological advancements. Our findings offer valuable insights for researchers seeking to improve their understanding of cellular dynamics through scRNA-seq analysis, ultimately fostering the development of more robust and widely applicable cell cycle identification methods.

Genome-wide association studies (GWAS) have successfully revealed many disease-associated genetic variants. For a case-control study, the adequate power of an association test can be achieved with a large sample size, although genotyping large samples is expensive. A cost-effective strategy to boost power is to integrate external control samples with publicly available genotyped data. However, the naive integration of external controls may inflate the type I error rates if ignoring the systematic differences (batch effect) between studies, such as the differences in sequencing platforms, genotype-calling procedures, population stratification, and so forth. To account for the batch effect, we propose an approach by integrating External Controls into the Association Test by Regression Calibration (iECAT-RC) in case-control association studies. Extensive simulation studies show that iECAT-RC not only can control type I error rates but also can boost statistical power in all models. We also apply iECAT-RC to the UK Biobank data for M72 Fibroblastic disorders by considering genotype calling as the batch effect. Four SNPs associated with fibroblastic disorders have been detected by iECAT-RC and the other two comparison methods, iECAT-Score and Internal. However, our method has a higher probability of identifying these significant SNPs in the scenario of an unbalanced case-control association study.

Spatial multi-omic studies have emerged as a promising approach to comprehensively analyze cells in tissues, enabling the joint analysis of multiple data modalities like transcriptome, epigenome, proteome, and metabolome in parallel or even the same tissue section. This review focuses on the recent advancements in spatial multi-omics technologies, including novel data modalities and computational approaches. We discuss the advancements in low-resolution and high-resolution spatial multi-omics methods which can resolve up to 10,000 of individual molecules at subcellular level. By applying and integrating these techniques, researchers have recently gained valuable insights into the molecular circuits and mechanisms which govern cell biology along the cardiovascular disease spectrum. We provide an overview of current data analysis approaches, with a focus on data integration of multi-omic datasets, highlighting strengths and weaknesses of various computational pipelines. These tools play a crucial role in analyzing and interpreting spatial multi-omics datasets, facilitating the discovery of new findings, and enhancing translational cardiovascular research. Despite nontrivial challenges, such as the need for standardization of experimental setups, data analysis, and improved computational tools, the application of spatial multi-omics holds tremendous potential in revolutionizing our understanding of human disease processes and the identification of novel biomarkers and therapeutic targets. Exciting opportunities lie ahead for the spatial multi-omics field and will likely contribute to the advancement of personalized medicine for cardiovascular diseases.

Glioblastoma (GBM) is the most aggressive and common malignant primary brain tumor; however, treatment remains a significant challenge. This study aims to identify drug repurposing or repositioning candidates for GBM by developing an integrative rare disease profile network containing heterogeneous types of biomedical data.
We developed a Glioblastoma-based Biomedical Profile Network (GBPN) by extracting and integrating biomedical information pertinent to GBM-related diseases from the NCATS GARD Knowledge Graph (NGKG). We further clustered the GBPN based on modularity classes which resulted in multiple focused subgraphs, named mc_GBPN. We then identified high-influence nodes by performing network analysis over the mc_GBPN and validated those nodes that could be potential drug repurposing or repositioning candidates for GBM.
We developed the GBPN with 1,466 nodes and 107,423 edges and consequently the mc_GBPN with forty-one modularity classes. A list of the ten most influential nodes were identified from the mc_GBPN. These notably include Riluzole, stem cell therapy, cannabidiol, and VK-0214, with proven evidence for treating GBM.
Our GBM-targeted network analysis allowed us to effectively identify potential candidates for drug repurposing or repositioning. Further validation will be conducted by using other different types of biomedical and clinical data and biological experiments. The findings could lead to less invasive treatments for glioblastoma while significantly reducing research costs by shortening the drug development timeline. Furthermore, this workflow can be extended to other disease areas.

Chronic kidney disease (CKD) was the 12th leading cause of death globally in 2017 with the prevalence of CKD estimated at ~9%. Early detection and intervention for CKD may improve patient outcomes, but standard testing approaches even in developed countries do not facilitate identification of patients at high risk of developing CKD, nor those progressing to end-stage kidney disease (ESKD). Recent advances in CKD research are moving towards a more personalised approach for CKD. Heritability for CKD ranges from 30% to 75%, yet identified genetic risk factors account for only a small proportion of the inherited contribution to CKD. More in depth analysis of genomic sequencing data in large cohorts is revealing new genetic risk factors for common diagnoses of CKD and providing novel diagnoses for rare forms of CKD. Multi-omic approaches are now being harnessed to improve our understanding of CKD and explain some of the so-called \'missing heritability\'. The most common omic analyses employed for CKD are genomics, epigenomics, transcriptomics, metabolomics, proteomics and phenomics. While each of these omics have been reviewed individually, considering integrated multi-omic analysis offers considerable scope to improve our understanding and treatment of CKD. This narrative review summarises current understanding of multi-omic research alongside recent experimental and analytical approaches, discusses current challenges and future perspectives, and offers new insights for CKD.

The pharmaceutical industry continuously looks for ways to improve its development and manufacturing efficiency. In recent years, such efforts have been driven by the transition from batch to continuous manufacturing and digitalization in process development. To facilitate this transition, integrated data management and informatics tools need to be developed and implemented within the framework of Industry 4.0 technology. In this regard, the work aims to guide the data integration development of continuous pharmaceutical manufacturing processes under the Industry 4.0 framework, improving digital maturity and enabling the development of digital twins. This paper demonstrates two instances where a data integration framework has been successfully employed in academic continuous pharmaceutical manufacturing pilot plants. Details of the integration structure and information flows are comprehensively showcased. Approaches to mitigate concerns in incorporating complex data streams, including integrating multiple process analytical technology tools and legacy equipment, connecting cloud data and simulation models, and safeguarding cyber-physical security, are discussed. Critical challenges and opportunities for practical considerations are highlighted.