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Zhijin Wu

Publications and source records attributed to Zhijin Wu.

10 recordsLinked to original sources
PubMed2007

Alternative statistical parameter for high-throughput screening assay quality assessment.

High-throughput screening is an essential process in drug discovery. The ability to identify true active compounds depends on the high quality of assays and proper analysis of data. The Z factor, presented by Zhang et al. in 1999, provides an easy and useful summary of assay quality and has been a widely accepted standard. However, as data analysis has undergone much improvement recently, the assessment of assay quality has not evolved in parallel. In this article, the authors study the implications of Z factor values under different conditions and link the Z factor with the power of discovering true active compounds. They discuss the different interpretations of Z factor depending on error distributions and advocate direct analysis of power as assay quality assessment. They also propose that in estimating assay quality parameters, adjustments in data analysis should be taken into account. Studying the power of identifying true "hits" gives a more direct interpretation of assay quality and may provide guidance in assay optimization on some occasions.

Chemistry, Pharmaceutical↗
PubMed2006

Comparison of Affymetrix GeneChip expression measures.

MOTIVATION: In the Affymetrix GeneChip system, preprocessing occurs before one obtains expression level measurements. Because the number of competing preprocessing methods was large and growing we developed a benchmark to help users identify the best method for their application. A webtool was made available for developers to benchmark their procedures. At the time of writing over 50 methods had been submitted. RESULTS: We benchmarked 31 probe set algorithms using a U95A dataset of spike in controls. Using this dataset, we found that background correction, one of the main steps in preprocessing, has the largest effect on performance. In particular, background correction appears to improve accuracy but, in general, worsen precision. The benchmark results put this balance in perspective. Furthermore, we have improved some of the original benchmark metrics to provide more detailed information regarding precision and accuracy. A handful of methods stand out as providing the best balance using spike-in data with the older U95A array, although different experiments on more current arrays may benchmark differently. AVAILABILITY: The affycomp package, now version 1.5.2, continues to be available as part of the Bioconductor project (http://www.bioconductor.org). The webtool continues to be available at http://affycomp.biostat.jhsph.edu CONTACT: rafa@jhu.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗
PubMed2004

A benchmark for Affymetrix GeneChip expression measures.

MOTIVATION: The defining feature of oligonucleotide expression arrays is the use of several probes to assay each targeted transcript. This is a bonanza for the statistical geneticist, who can create probeset summaries with specific characteristics. There are now several methods available for summarizing probe level data from the popular Affymetrix GeneChips, but it is difficult to identify the best method for a given inquiry. RESULTS: We have developed a graphical tool to evaluate summaries of Affymetrix probe level data. Plots and summary statistics offer a picture of how an expression measure performs in several important areas. This picture facilitates the comparison of competing expression measures and the selection of methods suitable for a specific investigation. The key is a benchmark data set consisting of a dilution study and a spike-in study. Because the truth is known for these data, we can identify statistical features of the data for which the expected outcome is known in advance. Those features highlighted in our suite of graphs are justified by questions of biological interest and motivated by the presence of appropriate data.

Algorithms↗
PubMed2003

Use of mixture models in a microarray-based screening procedure for detecting differentially represented yeast mutants.

We describe the use of a statistical model in a genome-wide microarray-based yeast genetic screen performed by imposing different genetic selections on thousands of yeast mutants in parallel. A mixture model is fitted to data obtained from oligonucleotide arrays hybridized to 20-mer oligonucleotide "barcodes'' and a procedure based on the fitted model is used to search for mutants differentially represented under experimental and control conditions. The fitted stochastic model provides a way to assess uncertainty. We demonstrate the usefulness of the model by applying it to the problem of screening for components of the nonhomologous end joining (NHEJ) pathway and identified known components of the NHEJ pathway.

Journal Article↗
PubMed2003

Influence of bladder outlet obstruction and detrusor contractility on residual urine in patients with benign prostatic hyperplasia.

OBJECTIVE: To study the relationship between the degree of bladder outlet obstruction (BOO), detrusor contractility and residual urine in patients suffering from benign prostatic hyperplasia (BPH). METHODS: In 181 patients with BPH, degree of BOO, detrusor contractility, residual urine caculated from cathetering combined with the difference between the filling and the voiding were recorded and analysized statistically using urodynamic technique. RESULTS: Residual urine increased when the detusor contractility was weakened (F = 12.134, P = 0.001). In patients wih severe BOO, there was no significant difference in residual urine (F = 2.386, P = 0.071). CONCLUSIONS: Increased residual urine is mainly resulted from decreased detrusor contractility. BOO has no significant influence on residual urine. Some patients with normal or weakened detrusor contractility may have more residual urine.

Aged↗
PubMed2002

Inhibition of caspases protects cerebellar granule cells of the weaver mouse from apoptosis and improves behavioral phenotype.

The homozygous mouse mutant weaver exhibits a massive loss of cerebellar granule neurons postnatally. The death of these cells is associated with a single amino acid mutation in the G protein-activated inwardly rectifying potassium channel, Girk2. Evidence suggests that both the mutated Girk2 channel and the calcium channel-associated N-methyl-d-aspartate receptor play important roles in the apoptotic death of weaver cerebellar granule cells, but the downstream events associated with this process are unknown. In this study, we demonstrate that the consequences of the mutation result in caspase activation. In addition, our results show that caspase inhibition in vivo decreases caspase activation and granule cell apoptosis and significantly improves behavioral deficits associated with the weaver's phenotype.

Animals↗
PubMed2002

Urodynamic analysis of non-improvement after prostatectomy.

OBJECTIVE: To study the factors that affect the prognosis of the patients with benign prostatic hypertrophy (BPH) after prostatectomy. METHODS: Using urodynamic methods, we studied 50 BPH patients with embarrassing outcomes after prostatectomy. RESULTS: Detrusor instability (Dl) appeared in 20 (40%) patients. Twelve (24%) patients suffered from weak contractility of the detrusor and 18 (36%) patients had bladder outlet obstruction. CONCLUSIONS: Dl, weak contractility of the detrusor and bladder outlet obstruction are the most frequent causes affecting the prognosis of BPH patients after prostatectomy. Urodynamics may play a significant role in the identification of the causes of unsatisfied prognosis of BPH patients.

Aged↗
PubMedDate not supplied

Stochastic models inspired by hybridization theory for short oligonucleotide arrays.

High density oligonucleotide expression arrays are a widely used tool for the measurement of gene expression on a large scale. Affymetrix GeneChip arrays appear to dominate this market. These arrays use short oligonucleotides to probe for genes in an RNA sample. Due to optical noise, nonspecific hybridization, probe-specific effects, and measurement error, ad hoc measures of expression that summarize probe intensities can lead to imprecise and inaccurate results. Various researchers have demonstrated that expression measures based on simple statistical models can provide great improvements over the ad hoc procedure offered by Affymetrix. Recently, physical models based on molecular hybridization theory have been proposed as useful tools for prediction of, for example, nonspecific hybridization. These physical models show great potential in terms of improving existing expression measures. In this paper, we suggest that the system producing the measured intensities is too complex to be fully described with these relatively simple physical models, and we propose empirically motivated stochastic models that complement the above-mentioned molecular hybridization theory to provide a comprehensive description of the data. We discuss how the proposed model can be used to obtain improved measures of expression useful for the data analysts.

Algorithms↗