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Arianne C Richard Paul A Lyons James E Peters Daniele Biasci Shaun M Flint James C Lee Eoin F McKinney Richard M Siegel Kenneth GC Smith 《BMC genomics》2014,15(1)
Background
Although numerous investigations have compared gene expression microarray platforms, preprocessing methods and batch correction algorithms using constructed spike-in or dilution datasets, there remains a paucity of studies examining the properties of microarray data using diverse biological samples. Most microarray experiments seek to identify subtle differences between samples with variable background noise, a scenario poorly represented by constructed datasets. Thus, microarray users lack important information regarding the complexities introduced in real-world experimental settings. The recent development of a multiplexed, digital technology for nucleic acid measurement enables counting of individual RNA molecules without amplification and, for the first time, permits such a study.Results
Using a set of human leukocyte subset RNA samples, we compared previously acquired microarray expression values with RNA molecule counts determined by the nCounter Analysis System (NanoString Technologies) in selected genes. We found that gene measurements across samples correlated well between the two platforms, particularly for high-variance genes, while genes deemed unexpressed by the nCounter generally had both low expression and low variance on the microarray. Confirming previous findings from spike-in and dilution datasets, this “gold-standard” comparison demonstrated signal compression that varied dramatically by expression level and, to a lesser extent, by dataset. Most importantly, examination of three different cell types revealed that noise levels differed across tissues.Conclusions
Microarray measurements generally correlate with relative RNA molecule counts within optimal ranges but suffer from expression-dependent accuracy bias and precision that varies across datasets. We urge microarray users to consider expression-level effects in signal interpretation and to evaluate noise properties in each dataset independently.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-649) contains supplementary material, which is available to authorized users. 相似文献3.
Background
Thyroid fine needle aspiration cytology (FNAC) is the standard diagnostic modality for thyroid nodules. However, it has limitations among which is the incidence of non-diagnostic results (Thy1). Management of cases with repeatedly non-diagnostic FNAC ranges from simple observation to surgical intervention. We aim to evaluate the incidence of malignancy in non-diagnostic FNAC, and the success rate of repeated FNAC. We also aim to evaluate risk factors for malignancy in patients with non-diagnostic FNAC.Materials and Methods
Retrospective analyses of consecutive cases with thyroid non diagnostic FNAC results were included.Results
Out of total 1657 thyroid FNAC done during the study period, there were 264 (15.9%) non-diagnostic FNAC on the first attempt. On repeating those, the rate of a non-diagnostic result on second FNAC was 61.8% and on third FNAC was 47.2%. The overall malignancy rate in Thy1 FNAC was 4.5% (42% papillary, 42% follicular and 8% anaplastic), and the yield of malignancy decreased considerably with successive non-diagnostic FNAC. Ultrasound guidance by an experienced head neck radiologist produced the lowest non-diagnostic rate (38%) on repetition compared to US guidance by a generalist radiologist (65%) and by non US guidance (90%).Conclusions
There is a low risk of malignancy in patients with a non-diagnostic FNAC result, commensurate to the risk of any nodule. The yield of malignancy decreased considerably with successive non-diagnostic FNAC. 相似文献4.
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Background
The goal of feature selection is to select useful features and simultaneously exclude garbage features from a given dataset for classification purposes. This is expected to bring reduction of processing time and improvement of classification accuracy.Methodology
In this study, we devised a new feature selection algorithm (CBFS) based on clearness of features. Feature clearness expresses separability among classes in a feature. Highly clear features contribute towards obtaining high classification accuracy. CScore is a measure to score clearness of each feature and is based on clustered samples to centroid of classes in a feature. We also suggest combining CBFS and other algorithms to improve classification accuracy.Conclusions/Significance
From the experiment we confirm that CBFS is more excellent than up-to-date feature selection algorithms including FeaLect. CBFS can be applied to microarray gene selection, text categorization, and image classification. 相似文献6.
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Background
We present a novel and systematic approach to analyze temporal microarray data. The approach includes normalization, clustering and network analysis of genes.Methodology
Genes are normalized using an error model based uniform normalization method aimed at identifying and estimating the sources of variations. The model minimizes the correlation among error terms across replicates. The normalized gene expressions are then clustered in terms of their power spectrum density. The method of complex Granger causality is introduced to reveal interactions between sets of genes. Complex Granger causality along with partial Granger causality is applied in both time and frequency domains to selected as well as all the genes to reveal the interesting networks of interactions. The approach is successfully applied to Arabidopsis leaf microarray data generated from 31,000 genes observed over 22 time points over 22 days. Three circuits: a circadian gene circuit, an ethylene circuit and a new global circuit showing a hierarchical structure to determine the initiators of leaf senescence are analyzed in detail.Conclusions
We use a totally data-driven approach to form biological hypothesis. Clustering using the power-spectrum analysis helps us identify genes of potential interest. Their dynamics can be captured accurately in the time and frequency domain using the methods of complex and partial Granger causality. With the rise in availability of temporal microarray data, such methods can be useful tools in uncovering the hidden biological interactions. We show our method in a step by step manner with help of toy models as well as a real biological dataset. We also analyse three distinct gene circuits of potential interest to Arabidopsis researchers. 相似文献8.
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Mingxing Yang Xiumin Li Zhibin Li Zhimin Ou Ming Liu Suhuan Liu Xuejun Li Shuyu Yang 《PloS one》2013,8(12)
Motivation
DNA microarray analysis is characterized by obtaining a large number of gene variables from a small number of observations. Cluster analysis is widely used to analyze DNA microarray data to make classification and diagnosis of disease. Because there are so many irrelevant and insignificant genes in a dataset, a feature selection approach must be employed in data analysis. The performance of cluster analysis of this high-throughput data depends on whether the feature selection approach chooses the most relevant genes associated with disease classes.Results
Here we proposed a new method using multiple Orthogonal Partial Least Squares-Discriminant Analysis (mOPLS-DA) models and S-plots to select the most relevant genes to conduct three-class disease classification and prediction. We tested our method using Golub’s leukemia microarray data. For three classes with subtypes, we proposed hierarchical orthogonal partial least squares-discriminant analysis (OPLS-DA) models and S-plots to select features for two main classes and their subtypes. For three classes in parallel, we employed three OPLS-DA models and S-plots to choose marker genes for each class. The power of feature selection to classify and predict three-class disease was evaluated using cluster analysis. Further, the general performance of our method was tested using four public datasets and compared with those of four other feature selection methods. The results revealed that our method effectively selected the most relevant features for disease classification and prediction, and its performance was better than that of the other methods. 相似文献10.
Sanford T Chung PH Reinish A Valera V Srinivasan R Linehan WM Bratslavsky G 《PloS one》2011,6(7):e21260
Purpose
To evaluate the accuracy of the sub-classification of renal cortical neoplasms using molecular signatures.Experimental Design
A search of publicly available databases was performed to identify microarray datasets with multiple histologic sub-types of renal cortical neoplasms. Meta-analytic techniques were utilized to identify differentially expressed genes for each histologic subtype. The lists of genes obtained from the meta-analysis were used to create predictive signatures through the use of a pair-based method. These signatures were organized into an algorithm to sub-classify renal neoplasms. The use of these signatures according to our algorithm was validated on several independent datasets.Results
We identified three Gene Expression Omnibus datasets that fit our criteria to develop a training set. All of the datasets in our study utilized the Affymetrix platform. The final training dataset included 149 samples represented by the four most common histologic subtypes of renal cortical neoplasms: 69 clear cell, 41 papillary, 16 chromophobe, and 23 oncocytomas. When validation of our signatures was performed on external datasets, we were able to correctly classify 68 of the 72 samples (94%). The correct classification by subtype was 19/20 (95%) for clear cell, 14/14 (100%) for papillary, 17/19 (89%) for chromophobe, 18/19 (95%) for oncocytomas.Conclusions
Through the use of meta-analytic techniques, we were able to create an algorithm that sub-classified renal neoplasms on a molecular level with 94% accuracy across multiple independent datasets. This algorithm may aid in selecting molecular therapies and may improve the accuracy of subtyping of renal cortical tumors. 相似文献11.
Thomas Fleischer Arnoldo Frigessi Kevin C Johnson Hege Edvardsen Nizar Touleimat Jovana Klajic Margit LH Riis Vilde D Haakensen Fredrik W?rnberg Bj?rn Naume ?slaug Helland Anne-Lise B?rresen-Dale J?rg Tost Brock C Christensen Vessela N Kristensen 《Genome biology》2014,15(8)
Background
Ductal carcinoma in situ (DCIS) of the breast is a precursor of invasive breast carcinoma. DNA methylation alterations are thought to be an early event in progression of cancer, and may prove valuable as a tool in clinical decision making and for understanding neoplastic development.Results
We generate genome-wide DNA methylation profiles of 285 breast tissue samples representing progression of cancer, and validate methylation changes between normal and DCIS in an independent dataset of 15 normal and 40 DCIS samples. We also validate a prognostic signature on 583 breast cancer samples from The Cancer Genome Atlas. Our analysis reveals that DNA methylation profiles of DCIS are radically altered compared to normal breast tissue, involving more than 5,000 genes. Changes between DCIS and invasive breast carcinoma involve around 1,000 genes. In tumors, DNA methylation is associated with gene expression of almost 3,000 genes, including both negative and positive correlations. A prognostic signature based on methylation level of 18 CpGs is associated with survival of breast cancer patients with invasive tumors, as well as with survival of patients with DCIS and mixed lesions of DCIS and invasive breast carcinoma.Conclusions
This work demonstrates that changes in the epigenome occur early in the neoplastic progression, provides evidence for the possible utilization of DNA methylation-based markers of progression in the clinic, and highlights the importance of epigenetic changes in carcinogenesis.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0435-x) contains supplementary material, which is available to authorized users. 相似文献12.
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Michael P. Moreau Shannon E. Bruse Rebecka Jornsten Yushi Liu Linda M. Brzustowicz 《PloS one》2013,8(4)
Objective
MicroRNAs (miRNAs) are endogenously expressed noncoding RNA molecules that are believed to regulate multiple neurobiological processes. Expression studies have revealed distinct temporal expression patterns in the developing rodent and porcine brain, but comprehensive profiling in the developing human brain has not been previously reported.Methods
We performed microarray and TaqMan-based expression analysis of all annotated mature miRNAs (miRBase 10.0) as well as 373 novel, predicted miRNAs. Expression levels were measured in 48 post-mortem brain tissue samples, representing gestational ages 14–24 weeks, as well as early postnatal and adult time points.Results
Expression levels of 312 miRNAs changed significantly between at least two of the broad age categories, defined as fetal, young, and adult.Conclusions
We have constructed a miRNA expression atlas of the developing human brain, and we propose a classification scheme to guide future studies of neurobiological function. 相似文献18.
Jesús Espinal-Enríquez Said Mu?oz-Montero Ivan Imaz-Rosshandler Aldo Huerta-Verde Carmen Mejía Enrique Hernández-Lemus 《BMC genomics》2015,16(1)