vcf2fhir: a utility to convert VCF files into HL7 FHIR format for genomics-EHR integration.

BACKGROUND: VCF formatted files are the lingua franca of next-generation sequencing, whereas HL7 FHIR is emerging as a standard language for electronic health record interoperability. A growing number of FHIR-based clinical genomics applications are emerging. Here, we describe an open source utility for converting variants from VCF format into HL7 FHIR format. RESULTS: vcf2fhir converts VCF variants into a FHIR Genomics Diagnostic Report. Conversion translates each VCF row into a corresponding FHIR-formatted variant in the generated report. In scope are simple variants (SNVs, MNVs, Indels), along with zygosity and phase relationships, for autosomes, sex chromosomes, and mitochondrial DNA. Input parameters include VCF file and genome build ('GRCh37' or 'GRCh38'); and optionally a conversion region that indicates the region(s) to convert, a studied region that lists genomic regions studied by the lab, and a non-callable region that lists studied regions deemed uncallable by the lab. Conversion can be limited to a subset of VCF by supplying genomic coordinates of the conversion region(s). If studied and non-callable regions are also supplied, the output FHIR report will include 'region-studied' observations that detail which portions of the conversion region were studied, and of those studied regions, which portions were deemed uncallable. We illustrate the vcf2fhir utility via two case studies. The first, 'SMART Cancer Navigator', is a web application that offers clinical decision support by linking patient EHR information to cancerous gene variants. The second, 'Precision Genomics Integration Platform', intersects a patient's FHIR-formatted clinical and genomic data with knowledge bases in order to provide on-demand delivery of contextually relevant genomic findings and recommendations to the EHR. CONCLUSIONS: Experience to date shows that the vcf2fhir utility can be effectively woven into clinically useful genomic-EHR integration pipelines. Additional testing will be a critical step towards the clinical validation of this utility, enabling it to be integrated in a variety of real world data flow scenarios. For now, we propose the use of this utility primarily to accelerate FHIR Genomics understanding and to facilitate experimentation with further integration of genomics data into the EHR.

Time course of neuroanatomical and functional recovery after bilateral pudendal nerve injury in female rats.

The pudendal nerve innervates the external urethral sphincter (EUS) and is among the tissues injured during childbirth, which may lead to symptoms of stress urinary incontinence (SUI). To understand the mechanisms of injury and repair, urethral leak-point pressure (LPP) was measured 4 days, 2 wk, or 6 wk after bilateral pudendal nerve crush. Morphometric changes in the distal nerve and EUS were examined by light and electron microscopy. To determine whether recovery resulted from pudendal neuroregeneration, LPP was measured before and after pudendal nerve transection 2 wk after nerve crush. LPP was significantly decreased 4 days after pudendal nerve crush compared with sham-injured animals as well as 2 or 6 wk after nerve crush. LPP was not significantly different 2 or 6 wk after nerve crush compared with sham-injured animals, suggesting that urethral function had returned to normal. Four days after pudendal nerve crush, the EUS branch of the pudendal nerve distal to the injury site showed evidence of nerve degeneration and the EUS appeared disrupted. Two weeks after nerve crush, the distal nerve and EUS both showed evidence of both nerve degeneration and recovery. Two weeks after nerve crush, LPP was significantly decreased after nerve transection. Six weeks after nerve injury, evidence of neuroregeneration was observed in the pudendal nerve and the EUS. This study has demonstrated that functional recovery and neuroregeneration are significant 2 wk after nerve crush, although by anatomical assessment, recovery appears incomplete, suggesting that 2 wk represents an early time point of initial neuroregeneration.

Short-term functional and neuroregenerative response of the urethra to ovariectomy and vaginal distension in female rats.

The objective of this study was to investigate the effects of ovariectomy (OVX) and vaginal distension (VD) on leak point pressure (LPP) and pudendal nerve regenerative response in the female rat. Twenty rats underwent OVX 3 days prior to either VD or sham distension. Seventeen rats did not receive OVX but underwent either VD or sham distension. Four days after distension, LPP testing was performed. In situ hybridization for beta(II) tubulin mRNA, an indicator of the neuroregenerative response, was performed on motoneurons of the pudendal nerve. In the non-OVX group, LPP was significantly decreased after VD. After OVX, the difference in LPP between VD and sham rats did not quite reach the level of statistical significance. There was a statistically significant interaction between the effects of OVX and VD on LPP. There was no significant difference in in situ hybridization results between any of the groups. No neuroregenerative response of motoneurons of the pudendal nerve was observed after either VD or OVX.

Predicting urethral area from video-urodynamics in women with voiding dysfunction.

AIMS: Mathematical models are useful for developing predictive parameters for characterizing the biomechanics of voiding dysfunction. The goal of this project was to test a one-dimensional steady flow model used to predict the minimum cross-sectional urethral area from urodynamic data. METHODS: Nine adult female subjects underwent video-urodynamic testing. By using Bernoulli's formula and the Torricelli theorem, the minimum urethral area was predicted from pressure and flow rate at the moment of maximum flow rate during voiding. This prediction was compared with the minimum cross-sectional area of the urethra, which was calculated from minimum urethral diameter as measured from fluoroscopy, assuming a circular cross-section. RESULTS: The maximum flow rate during voiding was 14.4 +/- 3.0 mL/sec. Mean bladder, abdominal, and detrusor pressures simultaneous with maximum flow rate were 63 +/- 7, 29 +/- 6, and 33 +/- 6 cm H(2)O, respectively. Mean minimum cross-sectional area of the urethra from fluoroscopy was 8.0 +/- 2.0 mm(2). Mean minimum cross-sectional area of the urethra predicted by the mathematical model was 5.0 +/- 1.0 mm(2) using bladder pressure and 7.0 +/- 2.0 mm(2) using detrusor pressure. There were no significant differences between the three cross-sectional area measures. However, when area predictions were expressed as percentage of fluoroscopic measurements, the estimate from detrusor pressure (97 +/- 13%) was significantly larger than the estimate from bladder pressure (69 +/- 7%). CONCLUSIONS: A steady flow model is accurate enough on average to describe urine flow in the urethra. However, it may not be sufficiently accurate to aid in diagnosis of individuals.