scholarly journals Integrating Genomics and Clinical Data for Statistical Analysis by Using GEnome MINIng (GEMINI) and Fast Healthcare Interoperability Resources (FHIR): System Design and Implementation

10.2196/19879 ◽  
2020 ◽  
Vol 22 (10) ◽  
pp. e19879
Author(s):  
Julian Gruendner ◽  
Nicolas Wolf ◽  
Lars Tögel ◽  
Florian Haller ◽  
Hans-Ulrich Prokosch ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Data Integration ◽  
Genome Mining ◽  
University Hospital ◽  
Gene Variants ◽  
1000 Genomes Project ◽  
Analysis Pipeline ◽  
1000 Genomes ◽  
The University ◽  
Ngs Data

Background The introduction of next-generation sequencing (NGS) into molecular cancer diagnostics has led to an increase in the data available for the identification and evaluation of driver mutations and for defining personalized cancer treatment regimens. The meaningful combination of omics data, ie, pathogenic gene variants and alterations with other patient data, to understand the full picture of malignancy has been challenging. Objective This study describes the implementation of a system capable of processing, analyzing, and subsequently combining NGS data with other clinical patient data for analysis within and across institutions. Methods On the basis of the already existing NGS analysis workflows for the identification of malignant gene variants at the Institute of Pathology of the University Hospital Erlangen, we defined basic requirements on an NGS processing and analysis pipeline and implemented a pipeline based on the GEMINI (GEnome MINIng) open source genetic variation database. For the purpose of validation, this pipeline was applied to data from the 1000 Genomes Project and subsequently to NGS data derived from 206 patients of a local hospital. We further integrated the pipeline into existing structures of data integration centers at the University Hospital Erlangen and combined NGS data with local nongenomic patient-derived data available in Fast Healthcare Interoperability Resources format. Results Using data from the 1000 Genomes Project and from the patient cohort as input, the implemented system produced the same results as already established methodologies. Further, it satisfied all our identified requirements and was successfully integrated into the existing infrastructure. Finally, we showed in an exemplary analysis how the data could be quickly loaded into and analyzed in KETOS, a web-based analysis platform for statistical analysis and clinical decision support. Conclusions This study demonstrates that the GEMINI open source database can be augmented to create an NGS analysis pipeline. The pipeline generates high-quality results consistent with the already established workflows for gene variant annotation and pathological evaluation. We further demonstrate how NGS-derived genomic and other clinical data can be combined for further statistical analysis, thereby providing for data integration using standardized vocabularies and methods. Finally, we demonstrate the feasibility of the pipeline integration into hospital workflows by providing an exemplary integration into the data integration center infrastructure, which is currently being established across Germany.

scholarly journals Integrating Genomics and Clinical Data for Statistical Analysis by Using GEnome MINIng (GEMINI) and Fast Healthcare Interoperability Resources (FHIR): System Design and Implementation (Preprint)

2020 ◽  
Author(s):  
Julian Gruendner ◽  
Nicolas Wolf ◽  
Lars Tögel ◽  
Florian Haller ◽  
Hans-Ulrich Prokosch ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Data Integration ◽  
Genome Mining ◽  
University Hospital ◽  
Gene Variants ◽  
1000 Genomes Project ◽  
Analysis Pipeline ◽  
1000 Genomes ◽  
The University ◽  
Ngs Data

BACKGROUND The introduction of next-generation sequencing (NGS) into molecular cancer diagnostics has led to an increase in the data available for the identification and evaluation of driver mutations and for defining personalized cancer treatment regimens. The meaningful combination of omics data, ie, pathogenic gene variants and alterations with other patient data, to understand the full picture of malignancy has been challenging. OBJECTIVE This study describes the implementation of a system capable of processing, analyzing, and subsequently combining NGS data with other clinical patient data for analysis within and across institutions. METHODS On the basis of the already existing NGS analysis workflows for the identification of malignant gene variants at the Institute of Pathology of the University Hospital Erlangen, we defined basic requirements on an NGS processing and analysis pipeline and implemented a pipeline based on the GEMINI (GEnome MINIng) open source genetic variation database. For the purpose of validation, this pipeline was applied to data from the 1000 Genomes Project and subsequently to NGS data derived from 206 patients of a local hospital. We further integrated the pipeline into existing structures of data integration centers at the University Hospital Erlangen and combined NGS data with local nongenomic patient-derived data available in Fast Healthcare Interoperability Resources format. RESULTS Using data from the 1000 Genomes Project and from the patient cohort as input, the implemented system produced the same results as already established methodologies. Further, it satisfied all our identified requirements and was successfully integrated into the existing infrastructure. Finally, we showed in an exemplary analysis how the data could be quickly loaded into and analyzed in KETOS, a web-based analysis platform for statistical analysis and clinical decision support. CONCLUSIONS This study demonstrates that the GEMINI open source database can be augmented to create an NGS analysis pipeline. The pipeline generates high-quality results consistent with the already established workflows for gene variant annotation and pathological evaluation. We further demonstrate how NGS-derived genomic and other clinical data can be combined for further statistical analysis, thereby providing for data integration using standardized vocabularies and methods. Finally, we demonstrate the feasibility of the pipeline integration into hospital workflows by providing an exemplary integration into the data integration center infrastructure, which is currently being established across Germany.

scholarly journals Mapping bias overestimates reference allele frequencies at theHLAgenes in the 1000 Genomes Project phase I data

2014 ◽  
Author(s):  
Debora Yoshihara Caldeira Brandt ◽  
Vitor Rezende da Costa Aguiar ◽  
Bárbara Domingues Bitarello ◽  
Kelly Nunes ◽  
Jérôme Goudet ◽  
...  
Keyword(s):  
Phase I ◽  
Allele Frequency ◽  
Population Genomics ◽  
1000 Genomes Project ◽  
Reference Allele ◽  
1000 Genomes ◽  
Hla Genes ◽  
Mapping Bias ◽  
Genomic Regions ◽  
Ngs Data

Next Generation Sequencing (NGS) technologies have become the standard for data generation in studies of population genomics, as the 1000 Genomes Project (1000G). However, these techniques are known to be problematic when applied to highly polymorphic genomic regions, such as the Human Leukocyte Antigen (HLA) genes. Because accurate genotype calls and allele frequency estimations are crucial to population genomics analises, it is important to assess the reliability of NGS data. Here, we evaluate the reliability of genotype calls and allele frequency estimates of the SNPs reported by 1000G (phase I) at five HLA genes (HLA-A, -B, -C, -DRB1, -DQB1 ). We take advantage of the availability of HLA Sanger sequencing of 930 of the 1,092 1000G samples, and use this as a gold standard to benchmark the 1000G data. We document that 18.6% of SNP genotype calls in HLA genes are incorrect, and that allele frequencies are estimated with an error higher than ??0.1 at approximately 25% of the SNPs in HLA genes. We found a bias towards overestimation of reference allele frequency for the 1000G data, indicating mapping bias is an important cause of error in frequency estimation in this dataset. We provide a list of sites that have poor allele frequency estimates, and discuss the outcomes of including those sites in different kinds of analyses. Since the HLA region is the most polymorphic in the human genome, our results provide insights into the challenges of using of NGS data at other genomic regions of high diversity.

scholarly journals A Comparative Statistical Analysis on the Incidence of Developmental, Inflammatory and Neoplastic Odontogenic Cysts—A Single Center Retrospective Analysis from Italy

Oral ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 15-22
Author(s):  
Antonio Barresi ◽  
Giacomo Oteri ◽  
Angela Alibrandi ◽  
Matteo Peditto ◽  
Silvia Rapisarda ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
University Hospital ◽  
Odontogenic Cysts ◽  
Age And Gender ◽  
Patient Gender ◽  
Male Patients ◽  
Comparative Statistical Analysis ◽  
And Gender ◽  
The University ◽  
Maxillary Region

The aim of this study was a comparative statistical analysis of three categories of maxillary odontogenic cysts, evaluating frequency in relation to localization (mandibular or maxillary region), age and gender of patients. The study was a retrospective cohort study conducted at the University Hospital of Messina. Three hundred and fifty-six maxillary odontogenic cysts were classified into 283 inflammatory, 43 developmental and 30 neoplastic cysts. Female patients are more affected by developmental odontogenic cysts, while male patients are more affected by inflammatory odontogenic cysts. Both the mandibular and maxillary regions were affected mainly by inflammatory odontogenic cysts; no significantly statistic relationship was found between lesions and age. A significant association between odontogenic cyst lesions and patient gender was found. No significant association between histological features of lesion and age of patient was observed, nor subtype of odontogenic disease and localization (mandibular or maxillary).

scholarly journals ANGPTL3 gene variants in subjects with familial combined hyperlipidemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. M. Bea ◽  
E. Franco-Marín ◽  
V. Marco-Benedí ◽  
E. Jarauta ◽  
I. Gracia-Rubio ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Genetic Variants ◽  
Monogenic Disease ◽  
Potential Contribution ◽  
Gene Variants ◽  
Loss Of Function ◽  
Familial Combined Hyperlipidemia ◽  
1000 Genomes Project ◽  
Gain Of Function ◽  
1000 Genomes

AbstractAngiopoietin-like 3 (ANGPTL3) plays an important role in lipid metabolism in humans. Loss-of-function variants in ANGPTL3 cause a monogenic disease named familial combined hypolipidemia. However, the potential contribution of ANGPTL3 gene in subjects with familial combined hyperlipidemia (FCHL) has not been studied. For that reason, the aim of this work was to investigate the potential contribution of ANGPTL3 in the aetiology of FCHL by identifying gain-of-function (GOF) genetic variants in the ANGPTL3 gene in FCHL subjects. ANGPTL3 gene was sequenced in 162 unrelated subjects with severe FCHL and 165 normolipemic controls. Pathogenicity of genetic variants was predicted with PredictSNP2 and FruitFly. Frequency of identified variants in FCHL was compared with that of normolipemic controls and that described in the 1000 Genomes Project. No GOF mutations in ANGPTL3 were present in subjects with FCHL. Four variants were identified in FCHL subjects, showing a different frequency from that observed in normolipemic controls: c.607-109T>C, c.607-47_607-46delGT, c.835+41C>A and c.*52_*60del. This last variant, c.*52_*60del, is a microRNA associated sequence in the 3′UTR of ANGPTL3, and it was present 2.7 times more frequently in normolipemic controls than in FCHL subjects. Our research shows that no GOF mutations in ANGPTL3 were found in a large group of unrelated subjects with FCHL.

scholarly journals Approach to the Airway in the Emergency Department (ED) and Intensive Care Unit (ICU) in a Portuguese University Hospital Center: a prospective observational study

2019 ◽  
Author(s):  
Tiago Cabral ◽  
Helena Figueira ◽  
Ricardo Oliveira ◽  
Ângela Mota ◽  
Irene Aragão ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Emergency Department ◽  
Intensive Care ◽  
Statistical Analysis ◽  
Observational Study ◽  
Airway Management ◽  
Prospective Observational Study ◽  
Orotracheal Intubation ◽  
University Hospital ◽  
The University

Abstract Background Airway management is a commonly performed procedure in the Emergency Department (ED) and Intensive Care Unit (ICU), being tracheal intubation the gold standard with relatively high rates of complications in these settings. The purpose of our study was to analyse the airway approach in our institution at ED and ICU identifying the main complications associated and taking notice of possible factors related to them. Methods Prospective observational study conducted between May and September 2014 in the ICU and ED of Santo Antonio Hospital, with the primary aim of identifying the main complications of the airway approach in the critical patient and secondary aim to take notice of possible factors related with complications of the airway approach related to technical skills of the operator, patient´s specificities and airway approach techniques. The statistical analysis was done in cooperation with the Medical Informatics and Biostatistics Department of the Faculty of Medicine of the University of Porto. P values <0.05 were considered significant for all hypothesis testing. The analysis was done using the statistical analysis program SPSS® v.21.0 Results A total of 182 patients were included, corresponding to 257 attempted tracheal intubations (ATI). The rate of successful first-pass orotracheal intubation was 67%. Complications related to ATI were reported in 30% of all attempts, being most frequently among residents (81%, p=0.001) and those with little experience in airway approach (46%, p<0.001). The majority of complications was failed intubation (18%). In the group with complications, relation with an identifiable obvious cause was seen in 87% of cases (p<0.001), the major being inexperience in 42% of operators with complications, instead of 1% in the group without complications (p<0.001). Conclusions Failed ATI and its complications are largely dependent on operator´s expertise. Factors related to patient, lack of appropriate equipment and inappropriate strategy delineation also play a role. Recognition of patients at particular risk of difficult airway management is crucial.

Symptomatic vascular complications after vascular closure device use following diagnostic and interventional catheterisation

VASA ◽  
2004 ◽  
Vol 33 (2) ◽  
pp. 78-81 ◽  
Author(s):  
Thalhammer ◽  
Aschwanden ◽  
Jeanneret ◽  
Labs ◽  
Jäger
Keyword(s):  
Current Literature ◽  
Vascular Complications ◽  
University Hospital ◽  
Closure Device ◽  
Ultrasound Guided ◽  
Vascular Closure Device ◽  
Device Use ◽  
Arterial Stenoses ◽  
The University ◽  
Stenotic Lesions

Background: Haemostatic puncture closure devices for rapid and effective hemostasis after arterial catheterisation are a comfortable alternative to manual compression. Implanting a collagen plug against the vessel wall may become responsible for other kind of vascular injuries i.e. thrombotic or stenotic lesions and peripheral embolisation. The aim of this paper is to report our clinically relevant vascular complications after Angio-Seal® and to discuss the results in the light of the current literature. Patients and methods: We report the symptomatic vascular complications in 17 of 7376 patients undergoing diagnostic or therapeutic catheterisation between May 2000 and March 2003 at the University Hospital Basel. Results: Most patients presented with ischaemic symptoms, arterial stenoses or occlusions and thrombotic lesions (n = 14), whereas pseudoaneurysms were extremely rare (n = 3). Most patients with ischaemic lesions underwent vascular surgery and all patients with a pseudoaneurysm were successfully treated by ultrasound-guided compression. Conclusions: Severe vascular complications after Angio-Seal® are rare, consistent with the current literature. There may be a shift from pseudoaneurysms to ischaemic lesions.

User Evaluation of an Integrated Medical Workstation for Clinical Data Analysis

1993 ◽  
Vol 32 (05) ◽  
pp. 365-372 ◽  
Author(s):  
T. Timmeis ◽  
J. H. van Bemmel ◽  
E. M. van Mulligen
Keyword(s):  
Data Analysis ◽  
Clinical Research ◽  
Clinical Data ◽  
University Hospital ◽  
User Evaluation ◽  
Scientific Staff ◽  
Medical Institutions ◽  
Clinical Data Analysis ◽  
Research Problems ◽  
The University

AbstractResults are presented of the user evaluation of an integrated medical workstation for support of clinical research. Twenty-seven users were recruited from medical and scientific staff of the University Hospital Dijkzigt, the Faculty of Medicine of the Erasmus University Rotterdam, and from other Dutch medical institutions; and all were given a written, self-contained tutorial. Subsequently, an experiment was done in which six clinical data analysis problems had to be solved and an evaluation form was filled out. The aim of this user evaluation was to obtain insight in the benefits of integration for support of clinical data analysis for clinicians and biomedical researchers. The problems were divided into two sets, with gradually more complex problems. In the first set users were guided in a stepwise fashion to solve the problems. In the second set each stepwise problem had an open counterpart. During the evaluation, the workstation continuously recorded the user’s actions. From these results significant differences became apparent between clinicians and non-clinicians for the correctness (means 54% and 81%, respectively, p = 0.04), completeness (means 64% and 88%, respectively, p = 0.01), and number of problems solved (means 67% and 90%, respectively, p = 0.02). These differences were absent for the stepwise problems. Physicians tend to skip more problems than biomedical researchers. No statistically significant differences were found between users with and without clinical data analysis experience, for correctness (means 74% and 72%, respectively, p = 0.95), and completeness (means 82% and 79%, respectively, p = 0.40). It appeared that various clinical research problems can be solved easily with support of the workstation; the results of this experiment can be used as guidance for the development of the successor of this prototype workstation and serve as a reference for the assessment of next versions.

Sharing of Worldwide Spread Knowledge Using Hypermedia Facilities & Fast Communication Protocols (Mosaic and World Wide Web): The Example of ExPASy

1995 ◽  
Vol 34 (01/02) ◽  
pp. 75-78 ◽  
Author(s):  
R. D. Appel ◽  
O. Golaz ◽  
Ch. Pasquali ◽  
J.-C. Sanchez ◽  
A. Bairoch ◽  
...  
Keyword(s):  
World Wide Web ◽  
World Wide ◽  
Relevant Literature ◽  
Communication Protocols ◽  
Laboratory Data ◽  
Central Element ◽  
University Hospital ◽  
New Information ◽  
The University ◽  
Link Information

Abstract:The sharing of knowledge worldwide using hypermedia facilities and fast communication protocols (i.e., Mosaic and World Wide Web) provides a growth capacity with tremendous versatility and efficacy. The example of ExPASy, a molecular biology server developed at the University Hospital of Geneva, is striking. ExPASy provides hypermedia facilities to browse through several up-to-date biological and medical databases around the world and to link information from protein maps to genome information and diseases. Its extensive access is open through World Wide Web. Its concept could be extended to patient data including texts, laboratory data, relevant literature findings, sounds, images and movies. A new hypermedia culture is spreading very rapidly where the international fast transmission of documents is the central element. It is part of the emerging new “information society”.

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