The Use of Design Specificity in Standardized Mean Difference for Analysis of High throughput RNA Interference Screens

Author(s):  
Karol Kozak
2007 ◽  
Vol 12 (4) ◽  
pp. 497-509 ◽  
Author(s):  
Xiaohua Douglas Zhang ◽  
Marc Ferrer ◽  
Amy S. Espeseth ◽  
Shane Douglas Marine ◽  
Erica M. Stec ◽  
...  

RNA interference (RNAi) high-throughput screening (HTS) has been hailed as the 2nd genomics wave following the 1st genomics wave of gene expression microarrays and single-nucleotide polymorphism discovery platforms. Following an RNAi HTS, the authors are interested in identifying short interfering RNA (siRNA) hits with large inhibition/activation effects. For hit selection, the z-score method and its variants are commonly used in primary RNAi HTS experiments. Recently, strictly standardized mean difference ( SSMD) has been proposed to measure the siRNA effect represented by the magnitude of difference between an siRNA and a negative reference group. The links between SSMD and d+-probability offer a clear interpretation of siRNA effects from a probability perspective. Hence, SSMD can be used as a ranking metric for hit selection. In this article, the authors investigated both the SSMD-based testing process and the use of SSMD as a ranking metric for hit selection in 2 primary siRNA HTS experiments. The analysis results showed that, as a ranking metric, SSMD was more stable and reliable than percentage inhibition and led to more robust hit selection results. Using the SSMD -based testing method, the false-negative rate can more readily be obtained. More important, the use of the SSMD-based method can result in a reduction in both the false-negative and false-positive rates. The applications presented in this article demonstrate that the SSMD method addresses scientific questions and fills scientific needs better than both percentage inhibition and the commonly used z-score method for hit selection. ( Journal of Biomolecular Screening 2007:497-509)


2011 ◽  
Vol 16 (7) ◽  
pp. 775-785 ◽  
Author(s):  
Xiaohua Douglas Zhang

Hit selection is the ultimate goal in many high-throughput screens. Various analytic methods are available for this purpose. Some commonly used ones are z score, z* score, strictly standardized mean difference (SSMD), SSMD*, and t statistic. It is critical to know how to use them correctly because the misusage of them can readily produce misleading results. Here, the author presents basic concepts, elaborates their commonality and difference, describes some common misusage that people should avoid, and uses simulated simple examples to illustrate how to use them correctly.


2021 ◽  
pp. 002203452110038
Author(s):  
C.E. Fernández ◽  
C.A. Maturana ◽  
S.I. Coloma ◽  
A. Carrasco-Labra ◽  
R.A. Giacaman

The dental profession has experienced a dramatic acceleration in the use of communication systems and information-based technologies over recent years, originating new paradigms for the prevention and promotion of oral health. The purpose of this systematic review was to determine the effect of teledentistry-based (telematic) strategies, reported in randomized controlled trials and quasi-randomized trials, with a focus on oral health prevention and promotion–related outcomes in patients of all ages. We searched Medline via PubMed, SCOPUS, and Web of Science from inception until August 2020, regardless of the language of publication. We selected studies for inclusion and conducted data extraction, assessed risk of bias (Cochrane tool), and evaluated the certainty of the evidence (GRADE approach) in duplicate and independently. Out of 898 potentially eligible references, we selected 43 for full-text screening, of which 19 studies proved eligible: 18 randomized controlled trials and 1 quasi-randomized study. Virtual interventions were mostly asynchronous via apps ( n = 9), text messages ( n = 9), or computer-aided learning ( n = 1). The use of teledentistry as compared with conventional strategies may result in a large reduction in the plaque index (standardized mean difference, −1.18; 95% CI, −1.54 to −0.82; I2 = 92%; low certainty) and will likely result in a large reduction in the gingival index (standardized mean difference, −2.17; 95% CI, −3.15 to −1.19; I2 = 97%; moderate certainty) and in the incidence of white spot lesions (risk ratio, 0.48; 95% CI, 0.35 to 0.66; I2 = 0%; moderate certainty), with an increased effect over time. Evidence suggests that teledentistry, particularly mHealth (messages and apps), is a promising clinical tool for preventing and promoting oral health, especially under the accelerated virtualization of dentistry. Future studies should include a broader spectrum of the population, including adults and elders, to better inform policy and implementation of teledentistry (PROSPERO: CRD42020192685).


2021 ◽  
Vol 42 (4) ◽  
pp. 283-292 ◽  
Author(s):  
Michael T. Werner ◽  
John V. Bosso

Background: Only a fraction of patients with allergic rhinitis receive allergen-specific immunotherapy (AIT). AIT is most commonly delivered subcutaneously in a series of injections over 3‐5 years. Common obstacles to completing this therapy include cost and inconvenience. Intralymphatic immunotherapy (ILIT) has been proposed as a faster alternative, which requires as few as three injections spaced 4 weeks apart. Objective: This systematic review and meta-analysis evaluated the current evidence that supports the use of ILIT for allergic rhinitis. Methods: Clinical trials were identified in the published literature by using an electronic search strategy and were evaluated by using a risk of bias tool. Treatment outcome (symptom scores, medication scores, and combined symptom and medication scores) and provocation testing results (nasal provocation and skin-prick testing) were included in a meta-analysis of standardized mean difference with subgrouping by using a random-effects model. Overall adverse event rates were tabulated, and overall risk ratios were calculated by using a random-effects model. Results: We identified 17 clinical trials that met eligibility criteria. The standardized mean difference of ILIT on the symptom and medication score was ‐0.72 (95% confidence interval [CI], ‐0.98 to ‐0.46; p < 0.0001) (n = 10). The standardized mean difference of ILIT on nasal provocation and skin-prick testing was ‐1.00 (95% CI, ‐1.38 to ‐0.61; p < 0.0001) (n = 7) and ‐0.73 (95% CI, ‐0.99 to ‐0.47; p < 0.0001) (n = 7), respectively. No statistically significant heterogeneity was detected. The overall adverse event rate was 39.5% for ILIT and 23.5% for placebo. Also, 98.4% of adverse events were mild. Conclusion: Our meta-analysis demonstrated that ILIT was safe, conferred desensitization to seasonal and nonseasonal allergens, alleviated allergic rhinitis symptoms, and reduced medication use. A larger randomized, double-blind, placebo controlled trial will be necessary for wider adaptation of this form of AIT.


2017 ◽  
Vol 158 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Hye Kyung Cho ◽  
In Joon Park ◽  
Ho Young Yoon ◽  
Se Hwan Hwang

Objectives The perioperative administration of magnesium is known to reduce postoperative morbidities in adults, such as pain, agitation, and laryngospasm. The objective is to assess the effects of perioperative magnesium as the adjuvant to tonsillectomy as compared with tonsillectomy in children. Data Source Five databases (PubMed, SCOPUS, Embase, Web of Science, Cochrane). Method Two authors independently searched databases up to January 2017. We compared perioperative magnesium administration (magnesium groups) with no administration of magnesium (control group). The following outcomes were measured: postoperative pain intensity, analgesics administration, or other morbidities (laryngospasm, agitation, postoperative bleeding) in the postoperative 24 hours. Additionally, to evaluate the discrepancy of effects according to different administration routes, subgroup analyses regarding effects according to systemic or local administration of magnesium were performed. Results Nine prospective randomized controlled studies (n = 615) that evaluated the effect of magnesium in children having undergone tonsillectomy met inclusion criteria. Compared with control group, the time for first analgesic requirement was significantly delayed in magnesium groups (standardized mean difference = 0.75; 95% CI, 0.20-1.31; P = .0079). Laryngospasm (log odds ratio = −1.09; 95% CI,−2.11 to −0.07; P = .0362) and agitation score (standardized mean difference = −0.67; 95% CI, −0.97 to −0.36; P < .0001) in the recovery room also significantly decreased in magnesium groups. In subgroup analyses regarding pain and laryngospasm-related measurements, local administration of magnesium was shown to be more effective at reducing postoperative morbidities. Conclusions Perioperative magnesium regardless of route may offer pain, agitation, and laryngospasm relief without adverse effects in pediatric tonsillectomy. Based on the high heterogeneity of results within some parameters, further studies need to be performed to affirm these results.


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