scholarly journals Hardy Weinberg Exact Test In Large Scale Variant Calling Quality Control

2016 ◽  
Author(s):  
Zhuoyi Huang ◽  
Navin Rustagi ◽  
Degui Zhi ◽  
L. Adrienne Cupples ◽  
Richard Gibbs ◽  
...  
Keyword(s):  
Quality Control ◽  
Sample Size ◽  
Large Scale ◽  
High Throughput Sequencing ◽  
Control Measure ◽  
Variant Calling ◽  
P Value ◽  
Empirical Constant ◽  
Exact Test ◽  
Novel Strategy

AbstractHardy Weinberg Equilibrium (HWE) test is widely used as a quality control measure to detect sequencing artifacts like mismapping, allelic dropout and biases. However, in the high throughput sequencing era, where the sample size is beyond a thousand scale, the utility of HWE test in reducing the false positive rate remains unclear. In this paper, we demonstrate that HWE test has limited power in identifying sequencing artifacts when the variant allele frequency is lower than 1% in a variant call set produced from more than five thousand whole genome sequenced samples from two homogeneous populations. We develop a novel strategy of implementing HWE filtering in which we incorporate site frequency spectrum information and determine the p-value cutoff which optimizes the tradeoff between sensitivity and specificity. The novel strategy is shown to outperform the exact test of HWE with an empirical constant p-value cutoff regardless of the sequencing sample size. We also present best practice recommendations for identifying possible sources of false positives from large sequencing datasets based on an analysis of intrinsic biases in the variant calling process. Our novel strategy of determining the HWE test p-value cutoff and applying the test to the common variants provides a practical approach for the variant level quality controls in the upcoming sequencing projects with tens to hundreds of thousand of samples.

Variant calling and quality control of large-scale human genome sequencing data

2019 ◽  
Vol 3 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Brandon Jew ◽  
Jae Hoon Sul
Keyword(s):  
Quality Control ◽  
Genome Sequencing ◽  
Genetic Variants ◽  
Large Scale ◽  
Variant Calling ◽  
Sequencing Data ◽  
Computational Approaches ◽  
Sequencing Errors ◽  
Human Genome Sequencing ◽  
Number Of Individuals

Abstract Next-generation sequencing has allowed genetic studies to collect genome sequencing data from a large number of individuals. However, raw sequencing data are not usually interpretable due to fragmentation of the genome and technical biases; therefore, analysis of these data requires many computational approaches. First, for each sequenced individual, sequencing data are aligned and further processed to account for technical biases. Then, variant calling is performed to obtain information on the positions of genetic variants and their corresponding genotypes. Quality control (QC) is applied to identify individuals and genetic variants with sequencing errors. These procedures are necessary to generate accurate variant calls from sequencing data, and many computational approaches have been developed for these tasks. This review will focus on current widely used approaches for variant calling and QC.

scholarly journals Oral Bacterial Microbiomes in Association with Potential Prediabetes Using Different Criteria of Diagnosis

2021 ◽  
Vol 18 (14) ◽  
pp. 7436
Author(s):  
Kornwipa Rungrueang ◽  
Suraphong Yuma ◽  
Chanita Tantipoj ◽  
Siribang-on Piboonniyom Khovidhunkit ◽  
Pornpoj Fuangtharnthip ◽  
...  
Keyword(s):  
Sample Size ◽  
High Throughput Sequencing ◽  
Small Sample Size ◽  
Demographic Data ◽  
Selection Criterion ◽  
Small Sample ◽  
P Value ◽  
Rrna Gene ◽  
Dental Patients ◽  
Potential Biomarker

This study aimed to find a potential biomarker that can be used to diagnose prediabetic condition by comparing the salivary bacterial microbiomes between Thai dental patients with normoglycemia (NG) and those with potential prediabetes (PPG) conditions. Thirty-three subjects were randomly recruited. Demographic data were collected along with oral examination and unstimulated salivary collections. The salivary bacterial microbiomes were identified by high-throughput sequencing on the V3–V4 region of the bacterial 16S rRNA gene. Microbiomes in this study were composed of 12 phyla, 19 classes, 29 orders, 56 families, 81 genera, and 184 species. To check the validity of the selection criterion for prediabetes, we adopted two separate criteria to divide samples into PPG and NG groups using glycated hemoglobin A1c (HbA1c) or fasting plasma glucose (FPG) levels. Using the HbA1c level resulted in the significant reduction of Alloprevotella, Neisseria, Rothia, and Streptococcus abundances in PPG compared with those in NG (p-value < 0.05). On the other hand, the abundance of Absconditabacteriales was significantly reduced whereas Leptotrichia, Stomatobaculum, and Ruminococcaceae increased in the PPG group when the samples were classified by the FPG level (p-value < 0.05). It is implied that the group classifying criterion should be carefully concerned when investigating relative abundances between groups. However, regardless of the criteria, Rothia is significantly dominant in the NG groups, suggesting that Rothia might be a potential prediabetic biomarker. Due to the small sample size of this study, further investigation with a larger sample size is necessary to ensure that Rothia can be a potential biomarker for prediabetes in Thai people.

Impact of the p-Value Threshold on Interpretation of Trial Outcomes in Obstetrics and Gynecology

2021 ◽  
Author(s):  
Ann M. Bruno ◽  
Ashley E. Shea ◽  
Brett D. Einerson ◽  
Torri D. Metz ◽  
Amanda A. Allshouse ◽  
...  
Keyword(s):  
Sample Size ◽  
Primary Outcome ◽  
A Priori ◽  
Sample Size Calculation ◽  
P Value ◽  
Chi Square ◽  
Level Of Evidence ◽  
Exact Test ◽  
Manual Search ◽  
Significance Threshold

Objective Randomized controlled trials (RCTs) are considered the highest level of evidence to inform clinical practice. However, the reproducibility crisis has raised concerns about the scientific rigor of published RCT findings. Some advocate for a lower p-value threshold. We aimed to review published OB/Gyn topical RCTs in three representative OB/Gyn journals and three high impact non-OB/Gyn journals to determine if their interpretations would change with adoption of a p-value threshold for significance of 0.005. Secondarily, we evaluated if there were differences in methodologic characteristics between those that did and did not lose significance. Study Design A manual search was performed to identify all OB/Gyn RCTs published in the selected journals between July 2017 and June 2019. Data were collected on primary outcome(s), methodology, and p-values. We determined the proportion of primary outcomes that would remain statistically significant with adoption of a p-value significance threshold of 0.005 versus be reinterpreted as “suggestive” (defined as p-value between 0.005 and 0.05). Chi-square or Fisher's exact test were used to compare study characteristics. Results Overall, 202 RCTs met inclusion criteria; 52% in obstetrics and 48% in gynecology. Of 90 studies considered significant with p <0.05 at the time of publication, 54.4% (n = 49) would maintain significant (p < 0.005), while 45.6% (n = 41) would become suggestive using the lower threshold. Most RCTs utilized a single (90.1%) versus composite (8.9%) primary outcome type, used an intent-to-treat analysis (73.3%), and studied a drug intervention (46.5%). Methodologically, 23.7% did not prespecify analysis type, 28.2% did not meet the pre-determined sample size, and 9.4% did not report an a priori sample size calculation. Studies maintaining significance were more likely to be international and report a funding source. Conclusion Adopting a p-value significance threshold of 0.005 would require reinterpretation of almost half of RCT results in the OB/Gyn literature. Highly variable methodological quality was identified. Key Points

Emotional Intelligence may have Association with Blood Groups

2020 ◽  
Author(s):  
Saifullah Shaikh
Keyword(s):  
Emotional Intelligence ◽  
Blood Group ◽  
Large Scale ◽  
Cross Sectional Study ◽  
Blood Groups ◽  
Altruistic Behavior ◽  
P Value ◽  
Cross Sectional ◽  
Mean Values ◽  
Exact Test

Background: Emotional intelligence (EI) can be described by means of capabilities possessed by a person to recognize feeling, and to manage emotions. For instance, active types of blood are O and B i.e. they are (belligerent and developing) On the other hand blood types A and AB are submissive i.e. (unchanging and unprogressive). The study aimed to find out the association between emotional intelligence and blood groups. Methods: A cross sectional study was carried out on 184 male and female students of a private university, Karachi. Blood group of these subjects was determined by using hematological and aseptic techniques and samples were collected through finger prick method acknowledged by the students. Results were recorded by applying the Fisher’s exact test and one way ANOVA to see the significance. Results: Self-awareness having highest mean score in O- group 17.00±1.00 with p-value of 0.011. In empathy blood group A+20.20±3.22 and O- 20.00±1.73 achieved highest mean values with p-value of 0.000, self-motivation level also got highest mean score in O- group 23.67±3.51with p-value of 0.035, managing relations level was highest observed in O- group 17.00±1.73 with p-value of 0.001. In addition, altruistic behavior found positive in O- blood group 8.67±0.58 with significant p-value of 0.000 among all students. Conclusion: Blood groups were identified significantly with different emotional intelligence level. The students having blood group O found to be more emotionally intelligent. However, large-scale studies are required in different parts of the world to explore the new aspects.

Quality Control of Data in a Large-Scale Cancer Register Program

1966 ◽  
Vol 05 (02) ◽  
pp. 67-74 ◽  
Author(s):  
W. I. Lourie ◽  
W. Haenszeland
Keyword(s):  
United States ◽  
Quality Control ◽  
Cancer Patients ◽  
Large Scale ◽  
The United States ◽  
Newly Diagnosed ◽  
Related Data ◽  
Cancer Register ◽  
Independent Review ◽  
End Results

Quality control of data collected in the United States by the Cancer End Results Program utilizing punchcards prepared by participating registries in accordance with a Uniform Punchcard Code is discussed. Existing arrangements decentralize responsibility for editing and related data processing to the local registries with centralization of tabulating and statistical services in the End Results Section, National Cancer Institute. The most recent deck of punchcards represented over 600,000 cancer patients; approximately 50,000 newly diagnosed cases are added annually.Mechanical editing and inspection of punchcards and field audits are the principal tools for quality control. Mechanical editing of the punchcards includes testing for blank entries and detection of in-admissable or inconsistent codes. Highly improbable codes are subjected to special scrutiny. Field audits include the drawing of a 1-10 percent random sample of punchcards submitted by a registry; the charts are .then reabstracted and recoded by a NCI staff member and differences between the punchcard and the results of independent review are noted.

Isolated Liner Revision for Total Knee Arthroplasty Instability: A Road That Should Remain Less Taken

2020 ◽  
Author(s):  
Jason D. Tegethoff ◽  
Rafael Walker-Santiago ◽  
William M. Ralston ◽  
James A. Keeney
Keyword(s):  
Total Knee Arthroplasty ◽  
Femoral Component ◽  
Knee Arthroplasty ◽  
Primary Total Knee Arthroplasty ◽  
P Value ◽  
Surgical Morbidity ◽  
Exact Test ◽  
Total Knee ◽  
Component Revision

AbstractIsolated polyethylene liner exchange (IPLE) is infrequently selected as a treatment approach for patients with primary total knee arthroplasty (TKA) prosthetic joint instability. Potential advantages of less immediate surgical morbidity, faster recovery, and lower procedural cost need to be measured against reoperation and re-revision risk. Few published studies have directly compared IPLE with combined tibial and femoral component revision to treat patients with primary TKA instability. After obtaining institutional review board (IRB) approval, we performed a retrospective comparison of 20 patients treated with IPLE and 126 patients treated with tibial and femoral component revisions at a single institution between 2011 and 2018. Patient demographic characteristics, medical comorbidities, time to initial revision TKA, and reoperation (90 days, <2 years, and >2 years) were assessed using paired Student's t-test or Fisher's exact test with a p-value <0.01 used to determine significance. Patients undergoing IPLE were more likely to undergo reoperation (60.0 vs. 17.5%, p = 0.001), component revision surgery (45.0 vs. 8.7%, p = 0.002), and component revision within 2 years (30.0 vs. 1.6%, p < 0.0001). Differences in 90-day reoperation (p = 0.14) and revision >2 years (p = 0.19) were not significant. Reoperation for instability (30.0 vs. 4.0%, p < 0.001) and infection (20.0 vs. 1.6%, p < 0.01) were both higher in the IPLE group. IPLE does not provide consistent benefits for patients undergoing TKA revision for instability. Considerations for lower immediate postoperative morbidity and cost need to be carefully measured against long-term consequences of reoperation, delayed component revision, and increased long-term costs of multiple surgical procedures. This is a level III, case–control study.

scholarly journals Genomic prediction for growth using a low-density SNP panel in dromedary camels

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Morteza Bitaraf Sani ◽  
Javad Zare Harofte ◽  
Mohammad Hossein Banabazi ◽  
Saeid Esmaeilkhanian ◽  
Ali Shafei Naderi ◽  
...  
Keyword(s):  
Body Weight ◽  
Birth Weight ◽  
Sample Size ◽  
Genetic Improvement ◽  
Growth Traits ◽  
P Value ◽  
Dromedary Camels ◽  
Genome Wide ◽  
A Genome ◽  
Daily Gain

AbstractFor thousands of years, camels have produced meat, milk, and fiber in harsh desert conditions. For a sustainable development to provide protein resources from desert areas, it is necessary to pay attention to genetic improvement in camel breeding. By using genotyping-by-sequencing (GBS) method we produced over 14,500 genome wide markers to conduct a genome- wide association study (GWAS) for investigating the birth weight, daily gain, and body weight of 96 dromedaries in the Iranian central desert. A total of 99 SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.002). Genomic breeding values (GEBVs) were estimated with the BGLR package using (i) all 14,522 SNPs and (ii) the 99 SNPs by GWAS. Twenty-eight SNPs were associated with birth weight, daily gain, and body weight (p-value < 0.001). Annotation of the genomic region (s) within ± 100 kb of the associated SNPs facilitated prediction of 36 candidate genes. The accuracy of GEBVs was more than 0.65 based on all 14,522 SNPs, but the regression coefficients for birth weight, daily gain, and body weight were 0.39, 0.20, and 0.23, respectively. Because of low sample size, the GEBVs were predicted using the associated SNPs from GWAS. The accuracy of GEBVs based on the 99 associated SNPs was 0.62, 0.82, and 0.57 for birth weight, daily gain, and body weight. This report is the first GWAS using GBS on dromedary camels and identifies markers associated with growth traits that could help to plan breeding program to genetic improvement. Further researches using larger sample size and collaboration of the camel farmers and more profound understanding will permit verification of the associated SNPs identified in this project. The preliminary results of study show that genomic selection could be the appropriate way to genetic improvement of body weight in dromedary camels, which is challenging due to a long generation interval, seasonal reproduction, and lack of records and pedigrees.

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