Browsing by Subject "database"
Now showing 1 - 4 of 4
Results Per Page
Sort Options
Item Open Access A computational screen for site selective A-to-I editing detects novel sites in neuron specific Hu proteins(2010) Ensterö, Mats; Akerborg, Orjan; Lundin, Daniel; Wang, Bei; Furey, Terrence S; Ohman, Marie; Lagergren, JensBackground: Several bioinformatic approaches have previously been used to find novel sites of ADAR mediated A-to-I RNA editing in human. These studies have discovered thousands of genes that are hyper-edited in their non-coding intronic regions, especially in alu retrotransposable elements, but very few substrates that are site-selectively edited in coding regions. Known RNA edited substrates suggest, however, that site selective A-to-I editing is particularly important for normal brain development in mammals. Results: We have compiled a screen that enables the identification of new sites of site-selective editing, primarily in coding sequences. To avoid hyper-edited repeat regions, we applied our screen to the alu-free mouse genome. Focusing on the mouse also facilitated better experimental verification. To identify candidate sites of RNA editing, we first performed an explorative screen based on RNA structure and genomic sequence conservation. We further evaluated the results of the explorative screen by determining which transcripts were enriched for A-G mismatches between the genomic template and the expressed sequence since the editing product, inosine (I), is read as guanosine (G) by the translational machinery. For expressed sequences, we only considered coding regions to focus entirely on re-coding events. Lastly, we refined the results from the explorative screen using a novel scoring scheme based on characteristics for known A-to-I edited sites. The extent of editing in the final candidate genes was verified using total RNA from mouse brain and 454 sequencing. Conclusions: Using this method, we identified and confirmed efficient editing at one site in the Gabra3 gene. Editing was also verified at several other novel sites within candidates predicted to be edited. Five of these sites are situated in genes coding for the neuron-specific RNA binding proteins HuB and HuD.Item Open Access A database of 40 patient-based computational models for benchmarking organ dose estimates in CT.(Medical physics, 2020-07-06) Samei, Ehsan; Ria, Francesco; Tian, Xiaoyu; Segars, Paul WPURPOSE:Patient radiation burden in CT can best be characterized through risk estimates derived from organ doses. Organ doses can be estimated by Monte Carlo simulations of the CT procedures on computational phantoms assumed to emulate the patients. However, the results are subject to uncertainties related to how accurately the patient and CT procedure are modeled. Different methods can lead to different results. This paper, based on decades of organ dosimetry research, offers a database of CT scans, scan specifics, and organ doses computed using a validated Monte Carlo simulation of each patient and acquisition. It is aimed that the database can serve as means to benchmark different organ dose estimation methods against a benchmark dataset. ACQUISITION AND VALIDATION METHODS:Organ doses were estimated for 40 adult patients (22 female, 18 female) who underwent Chest and Abdominopelvic CT examinations. Patient-based computational models were created for each patient including 26 organs for female and 25 organs for male cases. A Monte Carlo code, previously validated experimentally, was applied to calculate organ doses under constant and two modulated tube current conditions. DATA FORMAT AND USAGE NOTES:The generated database reports organ dose values for Chest and Abdominopelvic examinations per patient and imaging condition. Patient information and images and scan specifications (energy spectrum, bowtie filter specification, and tube current profiles) are provided. The database is available at publicly accessible digital repositories. POTENTIAL APPLICATIONS:Consistency in patient risk estimation, and associated justification and optimization requires accuracy and consistency in organ dose estimation. The database provided in this paper is a helpful tool to benchmark different organ dose estimation methodologies to facilitate comparisons, assess uncertainties, and improve assessment of risk of CT scans based on organ dose.Item Open Access Assessing the differences in characteristics of patients lost to follow-up at 2 years: results from the Quality Outcomes Database study on outcomes of surgery for grade I spondylolisthesis.(Journal of neurosurgery. Spine, 2020-02) Bisson, Erica F; Mummaneni, Praveen V; Knightly, John; Alvi, Mohammed Ali; Goyal, Anshit; Chan, Andrew K; Guan, Jian; Biase, Michael; Strauss, Andrea; Glassman, Steven; Foley, Kevin; Slotkin, Jonathan R; Potts, Eric; Shaffrey, Mark; Shaffrey, Christopher I; Haid, Regis W; Fu, Kai-Ming; Wang, Michael Y; Park, Paul; Asher, Anthony L; Bydon, MohamadOBJECTIVE:Loss to follow-up has been shown to bias outcomes assessment among studies utilizing clinical registries. Here, the authors analyzed patients enrolled in a national surgical registry and compared the baseline characteristics of patients captured with those lost to follow-up at 2 years. METHODS:The authors queried the Quality Outcomes Database for patients with grade I lumbar degenerative spondylolisthesis undergoing a surgical intervention between July 2014 and June 2016. Only those patients enrolled in a multisite study investigating the impact of fusion on clinical and patient-reported outcomes (PROs) among patients with grade I spondylolisthesis were evaluated. RESULTS:Of the 608 patients enrolled in the study undergoing 1- or 2-level decompression (23.0%, n = 140) or 1-level fusion (77.0%, n = 468), 14.5% (n = 88) were lost to follow-up at 2 years. Patients who were lost to follow-up were more likely to be younger (59.6 ± 13.5 vs 62.6 ± 11.7 years, p = 0.031), be employed (unemployment rate: 53.3% [n = 277] for successful follow-up vs 40.9% [n = 36] for those lost to follow-up, p = 0.017), have anxiety (26.1% [n = 23] vs 16.3% [n = 85], p = 0.026), have higher back pain scores (7.4 ± 2.9 vs 6.6 ± 2.8, p = 0.010), have higher leg pain scores (7.4 ± 2.5 vs 6.4 ± 2.9, p = 0.003), have higher Oswestry Disability Index scores (50.8 ± 18.7 vs 46 ± 16.8, p = 0.018), and have lower EQ-5D scores (0.481 ± 0.2 vs 0.547 ± 0.2, p = 0.012) at baseline. CONCLUSIONS:To execute future, high-quality studies, it is important to identify patients undergoing surgery for spondylolisthesis who might be lost to follow-up. In a large, prospective registry, the authors found that those lost to follow-up were more likely to be younger, be employed, have anxiety disorder, and have worse PRO scores.Item Open Access Detection of Alternative Splice Variants at the Proteome Level in Aspergillus flavus(2010) Chang, Kung-Yen; Georgianna, D Ryan; Heber, Steffen; Payne, Gary A; Muddiman, David CIdentification of proteins from proteolytic peptides or intact proteins plays an essential role in proteomics. Researchers use search engines to match the acquired peptide sequences to the target proteins. However, search engines depend on protein databases to provide candidates for consideration. Alternative splicing (AS), the mechanism where the exon of pre-mRNAs can be spliced and rearranged to generate distinct mRNA and therefore protein variants, enable higher eukaryotic organisms, with only a limited number of genes, to have the requisite complexity and diversity at the proteome level. Multiple alternative isoforms from one gene often share common segments of sequences. However, many protein databases only include a limited number of isoforms to keep minimal redundancy. As a result, the database search might not identify a target protein even with high quality tandem MS data and accurate intact precursor ion mass. We computationally predicted an exhaustive list of putative isoforms of Aspergillus flavus proteins from 20 371 expressed sequence tags to investigate whether an alternative splicing protein database can assign a greater proportion of mass spectrometry data. The newly constructed AS database provided 9807 new alternatively spliced variants in addition to 12 832 previously annotated proteins. The searches of the existing tandem MS spectra data set using the AS database identified 29 new proteins encoded by 26 genes. Nine fungal genes appeared to have multiple protein isoforms. In addition to the discovery of splice variants, AS database also showed potential to improve genome annotation. In summary, the introduction of an alternative splicing database helps identify more proteins and unveils more information about a proteome.