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Chunlei Wu

Publications and source records attributed to Chunlei Wu.

5 recordsLinked to original sources
PubMed2005

Sequence dependence of cross-hybridization on short oligo microarrays.

One of the critical problems in the short oligo microarray technology is how to deal with cross-hybridization that produces spurious data. Little is known about the details of cross-hybridization effect at molecular level. Here, we report a free energy analysis of cross-hybridization on short oligo microarrays using data from a spike-in study. Our analysis revealed that cross-hybridization on the arrays is mostly caused by oligo fragments with a run of 10-16 nt complementary to the probes. Mismatches were estimated to be energetically much more costly in cross-hybridization than that in gene-specific hybridization, implying that the sources of cross-hybridization must be very different between a PM-MM probe pair. Consequently, it is unreliable to use MM probe signal to track cross-hybridizing signal on a corresponding PM probe. Our results also showed that the oligo fragments tend to bind to the 5' ends of the probes, and are rarely seen at the 3' ends. These results are useful for microarray design and data analysis.

Base Pair Mismatch↗
PubMed2005

Applications of beta-mixture models in bioinformatics.

SUMMARY: We propose a beta-mixture model approach to solve a variety of problems related to correlations of gene-expression levels. For example, in meta-analyses of microarray gene-expression datasets, a threshold value of correlation coefficients for gene-expression levels is used to decide whether gene-expression levels are strongly correlated across studies. Ad hoc threshold values such as 0.5 are often used. In this paper, we use a beta-mixture model approach to divide the correlation coefficients into several populations so that the large correlation coefficients can be identified. Another important application of the proposed method is in finding co-expressed genes. Two examples are provided to illustrate both applications. Through our analysis, we also discover that the popular model selection criteria BIC and AIC are not suitable for the beta-mixture model. To determine the number of components in the mixture model, we suggest an alternative criterion, ICL-BIC, which is shown to perform better in selecting the correct mixture model. SUPPLEMENTARY INFORMATION: http://odin.mdacc.tmc.edu/~yuanj/highcorgeneanno.html.

Animals↗
PubMed2004

Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis.

BACKGROUND: Metastatic disease is a major adverse prognostic factor in breast carcinoma. Lymph node metastases often represent the first step in the metastatic process. METHODS: To gain insight into the molecular events that underlie breast carcinoma metastasis, the authors compared gene expression profiles, obtained by cDNA microarray analysis, of nine matched primary tumors and metastases after screening for enrichment of tumor cells. Statistical analysis identified genes that are expressed at elevated or decreased levels in metastases relative to the corresponding primary tumors. Multidimensional scaling analysis indicated that in terms of expression levels, primary tumors were tightly clustered, whereas metastases exhibited a greater spread; this finding points to the more heterogeneous nature of metastases. Among the differentially expressed entities were the invasion- and tissue modeling-related genes IGFBP5, fibronectin, and MMP2; the cell cycle regulatory gene cyclin D1; other genes, such as enolase 2; and an expressed sequence tag similar to angiopoietin 1. To validate and extend these initial findings, the authors constructed a tissue microarray consisting of 100 primary malignancies paired with their lymph node metastases. Antibodies for the IGFBP-5, fibronectin, MMP-2, cyclin D1, and MDM-2 proteins were used to stain tissue array sections. RESULTS: Consistent with microarray data, statistically significant overexpression of IGFBP-5, down-regulation of cyclin D1, and unchanged MDM-2 levels were observed in metastatic tumor cells. Nonetheless, although fibronectin and MMP2 mRNA expression levels were decreased in many metastasis specimens, expression levels of the corresponding proteins in the extracellular matrix were elevated in most metastases. Decreased expression of fibronectin and MMP2 in lymph node metastases was further confirmed by real-time polymerase chain reaction assays performed on five additional specimen pairs. CONCLUSIONS: The results of the current study suggest that extracellular matrix protein expression and nuclear gene expression are associated via a negative-feedback regulatory mechanism. Therefore, gene expression profiling and tissue array validation should be combined to elucidate molecular events associated with the metastatic process.

Breast Neoplasms↗
PubMed2002

Increased yield of total RNA from fine-needle aspirates for use in expression microarray analysis.

Fine-needle aspirate samples hold the potential for gaining valuable insight into the molecular details and prognostic indicators for certain types of cancer in a limited volume of relatively pure tumor cells. Although limited, such clinical samples can be used with high efficiency when analyzed in conjunction with gene-dense expression microarrays. For this reason, it is essential to retrieve as much high-quality genetic material as possible from each fine-needle aspirate sample. We have conducted a study to improve the efficiency of extracting high quality total RNA to use in microarray analysis from single ex vivo fine-needle aspirate samples of 11 breast cancers added to RNAlater RNA Stabilization Reagent immediately upon collection. Approximately half the total RNA from fine-needle aspirate samples of breast cancers was isolated from the supernatant, and that RNA had similar quality and gene expression profile to the RNA that was isolated from the corresponding cell pellet. We recommend that the supernatant not be discarded when extracting RNA from fine-needle aspirate samples stored in RNAlater.

Biopsy, Needle↗