Optimizing biomagnetic sensor performance through in silico diagnostics: A novel approach with BEST (Biomagnetism Evaluation via Simulated Testing)
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ABSTRACT:
SUBMITTER: Sun C
PROVIDER: S-EPMC11226959 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:Quality management and independent assessment of high-throughput sequencing-based virus diagnostics have not yet been established as a mandatory approach for ensuring comparable results. The sensitivity and specificity of viral high-throughput sequence data analysis are highly affected by bioinformatics processing using publicly available and custom tools and databases and thus differ widely between individuals and institutions. Here we present the results of the COMPARE [Collaborative Management Platform for Detection and Analyses of (Re-)emerging and Foodborne Outbreaks in Europe] in silico virus proficiency test. An artificial, simulated in silico data set of Illumina HiSeq sequences was provided to 13 different European institutes for bioinformatics analysis to identify viral pathogens in high-throughput sequence data. Comparison of the participants' analyses shows that the use of different tools, programs, and databases for bioinformatics analyses can impact the correct identification of viral sequences from a simple data set. The identification of slightly mutated and highly divergent virus genomes has been shown to be most challenging. Furthermore, the interpretation of the results, together with a fictitious case report, by the participants showed that in addition to the bioinformatics analysis, the virological evaluation of the results can be important in clinical settings. External quality assessment and proficiency testing should become an important part of validating high-throughput sequencing-based virus diagnostics and could improve the harmonization, comparability, and reproducibility of results. There is a need for the establishment of international proficiency testing, like that established for conventional laboratory tests such as PCR, for bioinformatics pipelines and the interpretation of such results.
| S-EPMC6663916 | biostudies-literature
Project description:Versatile, simple and efficient sample preparation is desirable for point-of-care testing of emerging diseases such as zoonoses, but current sample preparation assays are insensitive, labour-intensive and time-consuming and require multiple instruments. We developed a single-tube sample preparation approach involving direct pathogen enrichment and extraction from human specimens using diatomaceous earth (DE). Amine-modified DE was used to directly enrich a zoonotic pathogen, Brucella, in a large sample volume. Next, a complex of amine-modified DE and dimethyl suberimidate was used for nucleic acid extraction from the enriched pathogen. Using our single-tube approach, the pathogen can be enriched and extracted within 60min at a level of 1 colony formation unit (CFU) from a 1ml sample volume in the same tube. The performance of this approach is 10-100 times better than that of a commercial kit (102 to 103CFU/ml) but does not require a large centrifuge. Finally, we combined the single-tube approach with a bio-optical sensor for rapid and accurate zoonotic pathogen detection in human urine samples. Using the combination system, Brucella in human urine can be efficiently enriched (~ 8-fold) and the detection limit is enhanced by up to 100 times (1CFU/ml bacteria in urine) compared with the commercial kit. This combined system is fast and highly sensitive and thus represents a promising approach for disease diagnosis in the clinical setting.
| S-EPMC7127695 | biostudies-literature
Project description:Inappropriate water and fertilizer management can lead to unstable crop yields. Excessive fertilization can potentially cause soil degradation and nitrogen (N) leaching. The aim of this study was to explore the optimal N application rate on two wheat varieties with different nitrogen responding under limited water irrigation at three experimental sites in the Piedmont plain of the Taihang Mountains, China. A two-year field experiment was conducted to explore the effects of five N application rates (N0, N120, N180, N240, and N300) on winter wheat growth, leaf area index, aboveground biomass, grain yield, grain N accumulation, and net return. The results showed that N application rate significantly affected leaf area index, aboveground biomass, grain yield, and harvest index. Variety and variety × N rate interactions had a significant effect on few indicators. Compared with N0, N180 improved leaf area index, aboveground biomass, grain yield, and grain N accumulation. Compared with N240 and N300, N180 increased the harvest index and N harvest index, without significantly reducing grain yield or grain N accumulation, while enhancing a higher N use efficiency. Fertilizers applied in the ranges of 144.7-212.9 and 150.3-247.0 kg ha-1 resulted in the highest net return for the KN199 and JM585 varieties, respectively. Our study provides a sound theoretical basis for high-efficiency fertilizer utilization in sustainable winter wheat production in the Piedmont plains of the Taihang Mountains of China.
| S-EPMC8629221 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is a heterogenous group of malignancies originating in the biliary tree, and associated with poor prognosis. Until recently, treatment options have been limited to surgical resection, liver-directed therapies, and chemotherapy. Identification of actionable genomic alterations with biomarker testing has revolutionized the treatment paradigm for these patients. However, several challenges exist to the seamless adoption of precision medicine in patients with CCA, relating to a lack of awareness of the importance of biomarker testing, hurdles in tissue acquisition, and ineffective collaboration among the multidisciplinary team (MDT). To identify gaps in standard practices and define best practices, multidisciplinary hepatobiliary teams from the University of California (UC) Davis and UC Irvine were convened; discussions of the meeting, including optimal approaches to tissue acquisition for diagnosis and biomarker testing, communication among academic and community healthcare teams, and physician education regarding biomarker testing, are summarized in this review.
| S-EPMC8773504 | biostudies-literature
Project description: Not available
| S-EPMC2816163 | biostudies-literature
Project description:BackgroundThe use of next-generation sequencing approaches in clinical diagnostics has led to a tremendous increase in data and a vast number of variants of uncertain significance that require interpretation. Therefore, prediction of the effects of missense mutations using in silico tools has become a frequently used approach. Aim of this study was to assess the reliability of in silico prediction as a basis for clinical decision making in the context of hereditary breast and/or ovarian cancer.MethodsWe tested the performance of four prediction tools (Align-GVGD, SIFT, PolyPhen-2, MutationTaster2) using a set of 236 BRCA1/2 missense variants that had previously been classified by expert committees. However, a major pitfall in the creation of a reliable evaluation set for our purpose is the generally accepted classification of BRCA1/2 missense variants using the multifactorial likelihood model, which is partially based on Align-GVGD results. To overcome this drawback we identified 161 variants whose classification is independent of any previous in silico prediction. In addition to the performance as stand-alone tools we examined the sensitivity, specificity, accuracy and Matthews correlation coefficient (MCC) of combined approaches.ResultsPolyPhen-2 achieved the lowest sensitivity (0.67), specificity (0.67), accuracy (0.67) and MCC (0.39). Align-GVGD achieved the highest values of specificity (0.92), accuracy (0.92) and MCC (0.73), but was outperformed regarding its sensitivity (0.90) by SIFT (1.00) and MutationTaster2 (1.00). All tools suffered from poor specificities, resulting in an unacceptable proportion of false positive results in a clinical setting. This shortcoming could not be bypassed by combination of these tools. In the best case scenario, 138 families would be affected by the misclassification of neutral variants within the cohort of patients of the German Consortium for Hereditary Breast and Ovarian Cancer.ConclusionWe show that due to low specificities state-of-the-art in silico prediction tools are not suitable to predict pathogenicity of variants of uncertain significance in BRCA1/2. Thus, clinical consequences should never be based solely on in silico forecasts. However, our data suggests that SIFT and MutationTaster2 could be suitable to predict benignity, as both tools did not result in false negative predictions in our analysis.
| S-EPMC5870501 | biostudies-literature
Project description:IntroductionStrategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation.MethodsWe calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%.ResultsIn the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider.ConclusionsDiagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery.
| S-EPMC6545556 | biostudies-literature
Project description:Humans can learn simple new tasks very quickly. This ability suggests that people can reuse previously learned procedural knowledge when it applies to a new context. We have proposed a modeling approach based on this idea and used it to create a model of the attentional blink (AB). The main idea of the skill-based approach is that models are not created from scratch but, instead, built up from reusable pieces of procedural knowledge (skills). This approach not only provides an explanation for the fast learning of simple tasks but also shows much promise to improve certain aspects of cognitive modeling (e.g., robustness and generalizability). We performed two experiments, in order to collect empirical support for the model's prediction that the AB will disappear when the two targets are consolidated as a single chunk. Firstly, we performed an unsuccessful replication of a study reporting that the AB disappears when participants are instructed to remember the targets as a syllable. However, a subsequent experiment using easily combinable stimuli supported the model's prediction and showed a strongly reduced AB in a large group of participants. This result suggests that it is possible to avoid the AB with the right consolidation strategy. The skill-based approach allowed relating this finding to a general cognitive process, thereby demonstrating that incorporating this approach can be very helpful to generalize the findings of cognitive models, which otherwise tends to be rather difficult.
| S-EPMC8782399 | biostudies-literature
Project description:BackgroundOncolytic viruses are playing an increasingly important role in cancer immunotherapy applications. Given the preclinical and clinical efficacy of these virus-based therapeutics, there is a need for fast, simple, and inexpensive downstream processing methodologies to purify biologically active viral agents that meet the increasingly higher safety standards stipulated by regulatory authorities like the Food and Drug Administration and the European Agency for the Evaluation of Medicinal Products. However, the production of virus materials for clinical dosing of oncolytic virotherapies is currently limited-in quantity, quality, and timeliness-by current purification technologies. Adsorption of virus particles to solid phases provides a convenient and practical choice for large-scale fractionation and recovery of viruses from cell and media contaminants. Indeed, chromatography has been deemed the most promising technology for large-scale purification of viruses for biomedical applications. The implementation of new chromatography media has improved process performance, but low yields and long processing times required to reach the desired purity are still limiting.ResultsHere we report the development of an interference chromatography-based process for purifying high titer, clinical grade oncolytic Newcastle disease virus using NatriFlo® HD-Q membrane technology. This novel approach to optimizing chromatographic performance utilizes differences in molecular bonding interactions to achieve high purity in a single ion exchange step.ConclusionsWhen used in conjunction with membrane chromatography, this high yield method based on interference chromatography has the potential to deliver efficient, scalable processes to enable viable production of oncolytic virotherapies.
| S-EPMC7301511 | biostudies-literature
Project description:Given the global nature of the coronavirus disease 2019 (COVID-19) pandemic, the need for disease detection and expanding testing capacity remains critical priorities. This review discusses the technological advances in testing capability and methodology that are currently used or in development for detecting the novel coronavirus. We describe the current clinical diagnostics and technology, including molecular and serological testing approaches, for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) testing as well as address their advantages and limitations. Nucleic acid amplification technology for molecular diagnostics remains the gold standard for virus detection. We highlight alternative molecular detection techniques used for developing novel COVID-19 diagnostics on the horizon. Antibody response against SARS-CoV-2 remains poorly understood and proper validation of serology tests is necessary to demonstrate their accuracy and clinical utility. In order to bring the pandemic under control, we must speed up the development of rapid and widespread testing through improvements in clinical diagnostics and testing technology as well as access to these tools.
| S-EPMC7361586 | biostudies-literature