scholarly journals Evaluation of Bioinformatic Programmes for the Analysis of Variants within Splice Site Consensus Regions

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Rongying Tang ◽  
Debra O. Prosser ◽  
Donald R. Love
Keyword(s):  
In Silico ◽  
Receiver Operator Curve ◽  
Consensus Guidelines ◽  
Diagnostic Use ◽  
Novel Variants ◽  
Receiver Operator Curve Analysis ◽  
Site Consensus ◽  
Splice Junctions ◽  
Selection Of ◽  
Operator Curve

The increasing diagnostic use of gene sequencing has led to an expanding dataset of novel variants that lie within consensus splice junctions. The challenge for diagnostic laboratories is the evaluation of these variants in order to determine if they affect splicing or are merely benign. A common evaluation strategy is to use in silico analysis, and it is here that a number of programmes are available online; however, currently, there are no consensus guidelines on the selection of programmes or protocols to interpret the prediction results. Using a collection of 222 pathogenic mutations and 50 benign polymorphisms, we evaluated the sensitivity and specificity of four in silico programmes in predicting the effect of each variant on splicing. The programmes comprised Human Splice Finder (HSF), Max Entropy Scan (MES), NNSplice, and ASSP. The MES and ASSP programmes gave the highest performance based on Receiver Operator Curve analysis, with an optimal cut-off of score reduction of 10%. The study also showed that the sensitivity of prediction is affected by the level of conservation of individual positions, with in silico predictions for variants at positions -4 and +7 within consensus splice sites being largely uninformative.

scholarly journals Determining the Patient Acceptable Symptomatic State for Patients Undergoing Arthroscopic Partial Meniscectomy in the Knee

2017 ◽  
Vol 5 (3_suppl3) ◽  
pp. 2325967117S0012
Author(s):  
Thomas Zochowski ◽  
Tim Dwyer ◽  
Darrell Ogilvie-Harris ◽  
John S. Theodoropoulos ◽  
Daniel B. Whelan ◽  
...  
Keyword(s):  
Curve Analysis ◽  
Partial Meniscectomy ◽  
Consecutive Series ◽  
Receiver Operator Curve ◽  
Arthroscopic Partial Meniscectomy ◽  
Pain Subscale ◽  
Patient Reported ◽  
Receiver Operator Curve Analysis ◽  
Meniscal Pathology ◽  
Operator Curve

Objectives: Arthroscopic partial meniscectomy is one of the most commonly performed procedures in orthopaedic surgery. However, information on the threshold at which patients consider themselves to be well for patient reported outcome measures (PROMs) after this surgery remains limited. Our goal was to determine the patient acceptable symptomatic state (PASS) for the Knee Injury and Osteoarthritic Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) Subjective Knee Form, the Western Ontario Meniscal Evaluation Tool (WOMET) and the Marx Activity Scale (MAS) in patients with knee meniscal pathology who treated with partial knee meniscectomy. Methods: A consecutive series of patients with knee meniscal pathology treated with arthroscopic partial meniscectomy plus or minus intra-articular debridement were eligible. Other inclusion criteria were: a Kellegren-Lawrence Grade of 0-2, and ligamentous integrity. The KOOS (0-100, 5 subscales), IKDC (0-100), WOMET (0-100) and MAS (0-16) were administered at baseline and 12 months postoperatively. An external anchor question at 1 year postoperatively was utilized to determine PASS values: “Taking into account all the activities you have during your daily life, your level of pain, and also your functional impairment, do you consider that your current state is satisfactory?” A receiver operator curve analysis was used to determine the PASS value at which patients considered their status to be satisfactory. Results: There were 115 patients (mean ± SD age, 53.8 ± 12.0 years), and 57.3% were male. Based on a receiver operator curve analysis, the PASS values - at which patients considered their status to be satisfactory - at 1 year after surgery were 43 (KOOS-symptoms subscale), 83 (KOOS-pain subscale), 84 (KOOS-functions of daily living subscale), 75 (KOOS-function, sport and recreational activity subscale), 56 (KOOS-quality of life subscale), 56 (IKDC), 61 (WOMET), 7 (MAS). The PASS threshold was not affected by baseline scores across the different instruments and there was no relationship between baseline score and likelihood of achieving the PASS. Age and sex were not significantly related to the odds of achieving the PASS for any of the PROMs. Conclusion: This is the first study to determine PASS in four commonly used knee-related PROMs in patients undergoing arthroscopic partial meniscectomy. The findings can allow researchers and clinicians to determine if partial meniscectomy is meaningful to patients and will be helpful for responder analysis in future trials related to knee arthroscopy and the treatment of meniscal pathology.

scholarly journals How to Use Online Tools to Generate New Hypotheses for Mammary Gland Biology Research: A Case Study for Wnt7b

2021 ◽  
Author(s):  
Yorick Bernardus Cornelis van de Grift ◽  
Nika Heijmans ◽  
Renée van Amerongen
Keyword(s):  
Mammary Gland ◽  
In Silico ◽  
Online Tools ◽  
Mammary Gland Biology ◽  
User Friendly ◽  
In Silico Analyses ◽  
Biology Research ◽  
Selection Of

AbstractAn increasing number of ‘-omics’ datasets, generated by labs all across the world, are becoming available. They contain a wealth of data that are largely unexplored. Not every scientist, however, will have access to the required resources and expertise to analyze such data from scratch. Fortunately, a growing number of investigators is dedicating their time and effort to the development of user friendly, online applications that allow researchers to use and investigate these datasets. Here, we will illustrate the usefulness of such an approach. Using regulation of Wnt7b expression as an example, we will highlight a selection of accessible tools and resources that are available to researchers in the area of mammary gland biology. We show how they can be used for in silico analyses of gene regulatory mechanisms, resulting in new hypotheses and providing leads for experimental follow up. We also call out to the mammary gland community to join forces in a coordinated effort to generate and share additional tissue-specific ‘-omics’ datasets and thereby expand the in silico toolbox.

scholarly journals Co-Deregulated miRNA Signatures in Childhood Central Nervous System Tumors: In Search for Common Tumor miRNA-Related Mechanics

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3028
Author(s):  
George I. Lambrou ◽  
Apostolos Zaravinos ◽  
Maria Braoudaki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cns Tumors ◽  
Normal Brain ◽  
Cns Tumor ◽  
Different Types ◽  
Receiver Operator Curve Analysis ◽  
The Central Nervous System ◽  
Tumor Types ◽  
Operator Curve

Despite extensive experimentation on pediatric tumors of the central nervous system (CNS), related to both prognosis, diagnosis and treatment, the understanding of pathogenesis and etiology of the disease remains scarce. MicroRNAs are known to be involved in CNS tumor oncogenesis. We hypothesized that CNS tumors possess commonly deregulated miRNAs across different CNS tumor types. Aim: The current study aims to reveal the co-deregulated miRNAs across different types of pediatric CNS tumors. Materials: A total of 439 CNS tumor samples were collected from both in-house microarray experiments as well as data available in public databases. Diagnoses included medulloblastoma, astrocytoma, ependydoma, cortical dysplasia, glioblastoma, ATRT, germinoma, teratoma, yoc sac tumors, ocular tumors and retinoblastoma. Results: We found miRNAs that were globally up- or down-regulated in the majority of the CNS tumor samples. MiR-376B and miR-372 were co-upregulated, whereas miR-149, miR-214, miR-574, miR-595 and miR-765 among others, were co-downregulated across all CNS tumors. Receiver-operator curve analysis showed that miR-149, miR-214, miR-574, miR-595 and miR765 could distinguish between CNS tumors and normal brain tissue. Conclusions: Our approach could prove significant in the search for global miRNA targets for tumor diagnosis and therapy. To the best of our knowledge, there are no previous reports concerning the present approach.

scholarly journals Factors Associated With Intraoperative Conversion to Total Thyroidectomy in Benign Goiters

2019 ◽  
Vol 2 (1) ◽  
pp. 105-109
Author(s):  
Samuel Olatoke ◽  
Olayide Agodirin ◽  
Ganiyu Rahman ◽  
Benjamin Bolaji ◽  
Habeeb Olufemi
Keyword(s):  
Total Thyroidectomy ◽  
Nodular Goiter ◽  
Degenerative Changes ◽  
P Value ◽  
Receiver Operator Curve ◽  
Factors Associated ◽  
Patient Demographics ◽  
Partial Thyroidectomy ◽  
Intraoperative Conversion ◽  
Operator Curve

Background: Decision to undertake total thyroidectomy when gross inspection of the gland raises suspicion of widespread degenerative changes is often intraoperative. Knowing the factors associated with intraoperative conversion to total thyroidectomy may assist preoperative counselling. This study describes the probability of conversion to total thyroidectomy and factors associated with con-version among patients hitherto planned for partial thyroidectomy. Methods: We reviewed 191 records and extracted data on patient demographics, the pre-operative radiograph findings, the weight of excised gland and the operation performed. Descriptive and inferential statistics were performed. Receiver operator curve was used to assess for cut-off point. P-value was set at 0.05. Results: A total of 191 records was reviewed consisting of 181 females (94.8% 95% CI 90.6-97.5) and 10 males (5.2%, 95%CI 2.5-9.4). Only nodular goiters required conversion to total thyroidectomy. The over-all probability of total thyroidectomy was 11%(95% CI 7.0-16.3). The probability of total thyroidectomy in female was 10.5%(95% CI 6.4-16.9) while in male was 20%(95% CI2.5-55.6). The probability of total thyroidectomy in a female with nodular goiter was 8.1%(95% CI 4.8-13.5), compared to 28.6%(95% CI 3.7-71) in males. The risk of total thyroidectomy was associated with the weight of the excised gland. Conclusion: Only nodular goiters required intraoperative conversion to total thyroidecto-my and the probability of conversion was higher in males.

scholarly journals Differentiating combined pulmonary fibrosis and emphysema from pure emphysema: utility of late gadolinium-enhanced MRI

2020 ◽  
Vol 4 (1) ◽  
Author(s):  
Hannah Fleming ◽  
Simon M. Clifford ◽  
Aoife Haughey ◽  
Roisin MacDermott ◽  
Niall McVeigh ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Area Under The Curve ◽  
Resonance Imaging ◽  
High Resolution Computed Tomography ◽  
Antifibrotic Therapy ◽  
Control Subjects ◽  
Receiver Operator Curve Analysis ◽  
Healthy Control ◽  
Traction Bronchiectasis ◽  
Operator Curve

Abstract Background Differentiating combined pulmonary fibrosis with emphysema (CPFE) from pure emphysema can be challenging on high-resolution computed tomography (HRCT). This has antifibrotic therapy implications. Methods Twenty patients with suspected CPFE underwent late gadolinium-enhanced (LGE) thoracic magnetic resonance imaging (LGE-MRI) and HRCT. Data from twelve healthy control subjects from a previous study who underwent thoracic LGE-MRI were included for comparison. Quantitative LGE signal intensity (SI) was retrospectively compared in regions of fibrosis and emphysema in CPFE patients to similar lung regions in controls. Qualitative comparisons for the presence/extent of reticulation, honeycombing, and traction bronchiectasis between LGE-MRI and HRCT were assessed by two readers in consensus. Results There were significant quantitative differences in fibrosis SI compared to emphysema SI in CPFE patients (25.8, IQR 18.4–31.0 versus 5.3, IQR 5.0–8.1, p < 0.001). Significant differences were found between LGE-MRI and HRCT in the extent of reticulation (12.5, IQR 5.0–20.0 versus 25.0, IQR 15.0–26.3, p = 0.038) and honeycombing (5.0, IQR 0.0–10.0 versus 20.0, IQR 10.6–20.0, p = 0.001) but not traction bronchiectasis (10.0, IQR 5–15 versus 15.0, IQR 5–15, p = 0.878). Receiver operator curve analysis of fibrosis SI compared to similarly located regions in control subjects showed an area under the curve of 0.82 (p = 0.002). A SI cutoff of 19 yielded a sensitivity of 75% and specificity of 86% in differentiating fibrosis from similarly located regions in control subjects. Conclusion LGE-MRI can differentiate CPFE from pure emphysema and may be a useful adjunct test to HRCT in patients with suspected CPFE.

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