scholarly journals Assigning Significance in Label-Free Quantitative Proteomics to Include Single-Peptide-Hit Proteins with Low Replicates

2010 ◽  
Vol 2010 ◽  
pp. 1-15 ◽  
Author(s):  
Qingbo Li

When sample replicates are limited in a label-free proteomics experiment, selecting differentially regulated proteins with an assignment of statistical significance remains difficult for proteins with a single-peptide hit or a small fold-change. This paper aims to address this issue. An important component of the approach employed here is to utilize the rule of Minimum number of Permuted Significant Pairings (MPSP) to reduce false positives. The MPSP rule generates permuted sample pairings from limited analytical replicates and simply requires that a differentially regulated protein can be selected only when it is found significant in designated number of permuted sample pairings. Both a power law global error model with a signal-to-noise ratio statistic (PLGEM-STN) and a constant fold-change threshold were initially used to select differentially regulated proteins. But both methods were found not stringent enough to control the false discovery rate to 5% in this study. On the other hand, the combination of the MPSP rule with either of these two methods significantly reduces false positives with little effect on the sensitivity to select differentially regulated proteins including those with a single-peptide hit or with a <2-fold change.

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Anil Vishnu G. K. ◽  
Gayatri Gogoi ◽  
Bhagaban Behera ◽  
Saeed Rila ◽  
Annapoorni Rangarajan ◽  
...  

AbstractThe rapid and label-free diagnosis of malignancies in ex vivo breast biopsy tissues has significant utility in pathology laboratories and operating rooms. We report a MEMS-based platform integrated with microchips that performs phenotyping of breast biopsy tissues using electrothermal sensing. The microchip, fabricated on a silicon substrate, incorporates a platinum microheater, interdigitated electrodes (IDEs), and resistance temperature detectors (RTDs) as on-chip sensing elements. The microchips are integrated onto the platform using a slide-fit contact enabling quick replacement for biological measurements. The bulk resistivity (ρB), surface resistivity (ρS), and thermal conductivity (k) of deparaffinized and formalin-fixed paired tumor and adjacent normal breast biopsy samples from N = 8 patients were measured. For formalin-fixed samples, the mean ρB for tumors showed a statistically significant fold change of 4.42 (P = 0.014) when the tissue was heated from 25 °C to 37 °C compared to the adjacent normal tissue, which showed a fold change of 3.47. The mean ρS measurements also showed a similar trend. The mean k of the formalin-fixed tumor tissues was 0.309 ± 0.02 W m−1 K−1 compared to a significantly higher k of 0.563 ± 0.028 W m−1 K−1 for the adjacent normal tissues. A similar trend was observed in ρB,ρS, and k for the deparaffinized tissue samples. An analysis of a combination of ρB, ρS, and k using Fisher’s combined probability test and linear regression suggests the advantage of using all three parameters simultaneously for distinguishing tumors from adjacent normal tissues with higher statistical significance.


Author(s):  
D. C. Joy ◽  
R. D. Bunn

The information available from an SEM image is limited both by the inherent signal to noise ratio that characterizes the image and as a result of the transformations that it may undergo as it is passed through the amplifying circuits of the instrument. In applications such as Critical Dimension Metrology it is necessary to be able to quantify these limitations in order to be able to assess the likely precision of any measurement made with the microscope.The information capacity of an SEM signal, defined as the minimum number of bits needed to encode the output signal, depends on the signal to noise ratio of the image - which in turn depends on the probe size and source brightness and acquisition time per pixel - and on the efficiency of the specimen in producing the signal that is being observed. A detailed analysis of the secondary electron case shows that the information capacity C (bits/pixel) of the SEM signal channel could be written as :


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard J. Smith ◽  
Fernando Pérez-Cota ◽  
Leonel Marques ◽  
Matt Clark

AbstractBrillouin light scattering (BLS) is an emerging method for cell imaging and characterisation. It allows elasticity-related contrast, optical resolution and label-free operation. Phonon microscopy detects BLS from laser generated coherent phonon fields to offer an attractive route for imaging since, at GHz frequencies, the phonon wavelength is sub-optical. Using phonon fields to image single cells is challenging as the signal to noise ratio and acquisition time are often poor. However, recent advances in the instrumentation have enabled imaging of fixed and living cells. This work presents the first experimental characterisation of phonon-based axial resolution provided by the response to a sharp edge. The obtained axial resolution is up to 10 times higher than that of the optical system used to take the measurements. Validation of the results are obtained with various polymer objects, which are in good agreement with those obtained using atomic force microscopy. Edge localisation, and hence profilometry, of a phantom boundary is measured with accuracy and precision of approximately 60 nm and 100 nm respectively. Finally, 3D imaging of fixed cells in culture medium is demonstrated.


Author(s):  
Ismail El Ouargui ◽  
Said Safi ◽  
Miloud Frikel

The resolution of a Direction of Arrival (DOA) estimation algorithm is determined based on its capability to resolve two closely spaced signals. In this paper, authors present and discuss the minimum number of array elements needed for the resolution of nearby sources in several DOA estimation methods. In the real world, the informative signals are corrupted by Additive White Gaussian Noise (AWGN). Thus, a higher signal-to-noise ratio (SNR) offers a better resolution. Therefore, we show the performance of each method by applying the algorithms in different noise level environments.


2006 ◽  
Vol 45 (9) ◽  
pp. 1181-1189 ◽  
Author(s):  
D. S. Wilks

Abstract The conventional approach to evaluating the joint statistical significance of multiple hypothesis tests (i.e., “field,” or “global,” significance) in meteorology and climatology is to count the number of individual (or “local”) tests yielding nominally significant results and then to judge the unusualness of this integer value in the context of the distribution of such counts that would occur if all local null hypotheses were true. The sensitivity (i.e., statistical power) of this approach is potentially compromised both by the discrete nature of the test statistic and by the fact that the approach ignores the confidence with which locally significant tests reject their null hypotheses. An alternative global test statistic that has neither of these problems is the minimum p value among all of the local tests. Evaluation of field significance using the minimum local p value as the global test statistic, which is also known as the Walker test, has strong connections to the joint evaluation of multiple tests in a way that controls the “false discovery rate” (FDR, or the expected fraction of local null hypothesis rejections that are incorrect). In particular, using the minimum local p value to evaluate field significance at a level αglobal is nearly equivalent to the slightly more powerful global test based on the FDR criterion. An additional advantage shared by Walker’s test and the FDR approach is that both are robust to spatial dependence within the field of tests. The FDR method not only provides a more broadly applicable and generally more powerful field significance test than the conventional counting procedure but also allows better identification of locations with significant differences, because fewer than αglobal × 100% (on average) of apparently significant local tests will have resulted from local null hypotheses that are true.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Nelson Samesima ◽  
Carlos A Pastore ◽  
Luciana D de Matos ◽  
Fernanda F Fumagalli ◽  
Mariane V Ferreira ◽  
...  

Introduction. The widely known electrocardiographic criteria for diagnosing left ventricular hypertrophy (LVH) use QRS complex voltages to define whether there is left ventricle enlargement or not. Mild myocardial hypertrophy is detected in many professional athletes and this is a consequence of their daily intensity of training. Thus it is not unusual that athlete’s ECGs show large QRS voltages with normal hearts. Objective. To evaluate the applicability of the usual electrocardiographic criteria for LVH - Sokolow-Lyon, Romhilt-Estes, Cornell and Gubner - in a population of professional athletes. Methods. The four LVH criteria for diagnosing LVH were applied to analyse ECGs of 107 professional athletes (71% soccer players, 29% marathonists, all male, age 25± 10 years, training for 9± 8 years) by the same observer unaware of echocardiographic results. ECG was considered to be indicative of LVH if: Sokolow-Lyon ≥35mm (V 1or 2 S wave+V 5or 6 R wave); Romhilt-Estes score ≥5 points (frontal plane: R or S waves ≥ 20mm, horizontal plane: R or S waves ≥ 30mm, Morris indices, V 5or 6 strain pattern, left axis deviation ≥ − 30°, intrinsecoid deflection ≥ 0.04s, QRS duration ≥ 0.10s) ; Cornell ≥ 28mm (aV L R wave + V 3 S wave); Gubner ≥ 22mm (D I R wave + D III S wave). Hypertrophy was considered whenever: LV diastolic diameter ≥ 60mm and/or septum ≥ 13mm and/or LV posterior wall ≥ 13mm. Kruskal-Wallis was used to statistically analyse quantitative variables, corrected chi-square test for categorical variables. Significance level: p ≤ 0.05. Results. Romhilt-Estes showed the best results (75% sensitivity, 84% specificity, 16 false-positives, 1 false-negative), and was the only criteria with statistical significance (p = 0.047). Sokolow-Lyon showed 100% sensitivity, 15% specificity, p = 0.545, 88% false-positives, 0% false-negative. Cornell and Gubner showed 25% and 0% sensitivity, 95% and 99% specificity, p=0.205 and p = 0.449, respectively. Conclusion. In this male population of professional athletes, Romhilt-Estes score proved to be the best criterion for identifying left ventricular hypertrophy, while Sokolow-Lyon criterion did not discriminate normal from abnormal hearts. Cornell and Gubner criteria should not be used in this population because of their low sensitivity.


Entropy ◽  
2020 ◽  
Vol 22 (6) ◽  
pp. 668
Author(s):  
Samet Gelincik ◽  
Ghaya Rekaya-Ben Othman

This paper investigates the achievable per-user degrees-of-freedom (DoF) in multi-cloud based sectored hexagonal cellular networks (M-CRAN) at uplink. The network consists of N base stations (BS) and K ≤ N base band unit pools (BBUP), which function as independent cloud centers. The communication between BSs and BBUPs occurs by means of finite-capacity fronthaul links of capacities C F = μ F · 1 2 log ( 1 + P ) with P denoting transmit power. In the system model, BBUPs have limited processing capacity C BBU = μ BBU · 1 2 log ( 1 + P ) . We propose two different achievability schemes based on dividing the network into non-interfering parallelogram and hexagonal clusters, respectively. The minimum number of users in a cluster is determined by the ratio of BBUPs to BSs, r = K / N . Both of the parallelogram and hexagonal schemes are based on practically implementable beamforming and adapt the way of forming clusters to the sectorization of the cells. Proposed coding schemes improve the sum-rate over naive approaches that ignore cell sectorization, both at finite signal-to-noise ratio (SNR) and in the high-SNR limit. We derive a lower bound on per-user DoF which is a function of μ BBU , μ F , and r. We show that cut-set bound are attained for several cases, the achievability gap between lower and cut-set bounds decreases with the inverse of BBUP-BS ratio 1 r for μ F ≤ 2 M irrespective of μ BBU , and that per-user DoF achieved through hexagonal clustering can not exceed the per-user DoF of parallelogram clustering for any value of μ BBU and r as long as μ F ≤ 2 M . Since the achievability gap decreases with inverse of the BBUP-BS ratio for small and moderate fronthaul capacities, the cut-set bound is almost achieved even for small cluster sizes for this range of fronthaul capacities. For higher fronthaul capacities, the achievability gap is not always tight but decreases with processing capacity. However, the cut-set bound, e.g., at 5 M 6 , can be achieved with a moderate clustering size.


2013 ◽  
Vol 419 ◽  
pp. 517-520 ◽  
Author(s):  
Song Ying ◽  
Lei Wang ◽  
Wen Yuan Zhao

The solid-state nanopore sensor offers a versatile platform for the rapid, label-free electrical detection and analysis of single molecules, especially on DNA sequencing. However, the overall signal-to-noise ratio (SNA) is a major challenge in sequencing applications. In our work, two different fluid systems made by metal and plexiglass have been designed to improve the signal to noise ratio of the solid-state nanopore sensor. From the measurements on the noise power spectra with a variety of conditions, it is found that plexiglass fluid system coupled with shielding box produces a good quality of electric signals on nanopore sensors.


2009 ◽  
Vol 25 (6) ◽  
pp. 765-771 ◽  
Author(s):  
D. J. McCarthy ◽  
G. K. Smyth

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