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Biomedical subjects

Wuju Li

Publications and source records attributed to Wuju Li.

7 recordsLinked to original sources

Mprobe 2.0: computer-aided probe design for oligonucleotide microarray.

UNLABELLED: DNA chips have proven to be effective tools in detecting gene expression levels. Compared with DNA chips using complementary DNA as probes, oligonucleotide microarrays using oligonucleotides as probes have attracted great attention because of their well known advantages. The design of gene-specific probes for each target is essential to the development of oligonucleotide microarrays. We have previously reported the development of a probe design software termed Mprobe 1.0. Here, we present a new version of this software, termed Mprobe 2.0. Several new features are included in Mprobe 2.0. Firstly, a paradox-based sequence database management system has been developed and integrated into the software, which consequently allows interoperability with sequences in GenBank, EMBL, and FASTA formats. Secondly, in contrast to setting a fixed threshold for the secondary structure of probes in Mprobe 1.0 and other related software, Mprobe 2.0 employs a different method. After parameters such as GC type, probe melting temperature and GC contents have been evaluated, candidate probes are sorted by the free energy from high to low value, followed by specificity analysis. Thirdly, Mprobe 2.0 provides users with substantial parameter options in the visual mode. Mprobe 2.0 possesses an easier interface for users to manage sequences annotated in different formats and design the optimal probes for oligonucleotide microarrays and other applications. AVAILABILITY: The program is free for non-commercial users and can be downloaded from the web page http://www.biosun.org.cn/mprobe/ CONTACT: Wuju Li (wujuli@yahoo.com or liwj@nic.bmi.ac.cn).

Algorithms↗

An approach to studying lung cancer-related proteins in human blood.

Early stage lung cancer detection is the first step toward successful clinical therapy and increased patient survival. Clinicians monitor cancer progression by profiling tumor cell proteins in the blood plasma of afflicted patients. Blood plasma, however, is a difficult cancer protein assessment medium because it is rich in albumins and heterogeneous protein species. We report herein a method to detect the proteins released into the circulatory system by tumor cells. Initially we analyzed the protein components in the conditioned medium (CM) of lung cancer primary cell or organ cultures and in the adjacent normal bronchus using one-dimensional PAGE and nano-ESI-MS/MS. We identified 299 proteins involved in key cellular process such as cell growth, organogenesis, and signal transduction. We selected 13 interesting proteins from this list and analyzed them in 628 blood plasma samples using ELISA. We detected 11 of these 13 proteins in the plasma of lung cancer patients and non-patient controls. Our results showed that plasma matrix metalloproteinase 1 levels were elevated significantly in late stage lung cancer patients and that the plasma levels of 14-3-3 sigma, beta, and eta in the lung cancer patients were significantly lower than those in the control subjects. To our knowledge, this is the first time that fascin, ezrin, CD98, annexin A4, 14-3-3 sigma, 14-3-3 beta, and 14-3-3 eta proteins have been detected in human plasma by ELISA. The preliminary results showed that a combination of CD98, fascin, polymeric immunoglobulin receptor/secretory component and 14-3-3 eta had a higher sensitivity and specificity than any single marker. In conclusion, we report a method to detect proteins released into blood by lung cancer. This pilot approach may lead to the identification of novel protein markers in blood and provide a new method of identifying tumor biomarker profiles for guiding both early detection and therapy of human cancer.

Adolescent↗

RDfolder: a web server for prediction of RNA secondary structure.

Prediction of RNA secondary structure is important in the functional analysis of RNA molecules. The RDfolder web server described in this paper provides two methods for prediction of RNA secondary structure: random stacking of helical regions and helical regions distribution. The random stacking method predicts secondary structure by Monte Carlo simulations. The method of helical regions distribution predicts secondary structure based on the helices that appear most frequently in the set of structures, which are generated by the random stacking method. The RDfolder web server can be accessed at http://rna.cbi.pku.edu.cn.

Internet↗

SamCluster: an integrated scheme for automatic discovery of sample classes using gene expression profile.

MOTIVATION: Feature (gene) selection can dramatically improve the accuracy of gene expression profile based sample class prediction. Many statistical methods for feature (gene) selection such as stepwise optimization and Monte Carlo simulation have been developed for tissue sample classification. In contrast to class prediction, few statistical and computational methods for feature selection have been applied to clustering algorithms for pattern discovery. RESULTS: An integrated scheme and corresponding program SamCluster for automatic discovery of sample classes based on gene expression profile is presented in this report. The scheme incorporates the feature selection algorithms based on the calculation of CV (coefficient of variation) and t-test into hierarchical clustering and proceeds as follows. At first, the genes with their CV greater than the pre-specified threshold are selected for cluster analysis, which results in two putative sample classes. Then, significantly differentially expressed genes in the two putative sample classes with p-values < or = 0.01, 0.05, or 0.1 from t-test are selected for further cluster analysis. The above processes were iterated until the two stable sample classes were found. Finally, the consensus sample classes are constructed from the putative classes that are derived from the different CV thresholds, and the best putative sample classes that have the minimum distance between the consensus classes and the putative classes are identified. To evaluate the performance of the feature selection for cluster analysis, the proposed scheme was applied to four expression datasets COLON, LEUKEMIA72, LEUKEMIA38, and OVARIAN. The results show that there are only 5, 1, 0, and 0 samples that have been misclassified, respectively. We conclude that the proposed scheme, SamCluster, is an efficient method for discovery of sample classes using gene expression profile. AVAILABILITY: The related program SamCluster is available upon request or from the web page http://www.sph.uth.tmc.edu:8052/hgc/Downloads.asp.

Algorithms↗

[Antigenicity and physicochemical properties of two human NR1a polypeptides related to activation of NMDA receptor].

OBJECTIVE: To investigate the distribution of antigenic sites in two human NR1a polypeptides related to activation of N-methyl-D-aspartate receptor (NMDAR) and their physicochemical properties. METHODS: The amino acid sequences of two polypeptides, P1, a region containing 151 amino acid residues preceding the first transmembrane domain of the human NR1a, and P2 with 144 residues following the third transmembrane domain, were obtained from protein database by GOLDKEY software (4.0 version). Four parameters including Hopp-Woods and Kyte hydrophilicity, Janin accessibility, Karplus-Schulz flexibility, and Welling antigenicity were used to determine the antigenic sites, and Prosite programme and Chou-Fasman method were employed to analyze their related sequence motifs and the secondary structures. Finally, comparison of the comprehensive predictions with some of the available experimental information was made. RESULTS: There were about six and seven antigenic sites containing 8 approximately 15 residues in the P1 and P2 polypeptides respectively. The antigenic sites in P1 were mainly located in the amino terminal, but the ones in P2 were dispersed rather uniformly. Many sites in P2 polypeptide including some residues in its initial part, the amino terminal, showed higher hydrophilicity, accessibility, and antigenicity than those in P1. In addition, P1 and P1 were also different in the primary and secondary structure. P1 contained more cysteine residues and was rich in random coils, while P2 contained more aromatic residues and exhibited mainly helical structures. CONCLUSION: Both human NR1a polypeptides related to activation of NMDA receptor, P1 and P2, have a certain amount of antigenic sites. Compared with P1, P2 may be of higher antigenicity, and may be more easily used as a molecular target in immunization intervention to control the activation of NMDAR.

Amino Acid Motifs↗

MProbe: computer aided probe design for oligonucleotide microarrays.

The present work describes a complete probe design software system for oligonucleotide microarrays based on Kane's research on probe sensitivity and specificity (Kane's rule). Combining Kane's rule and traditional criteria for probe design we constructed MProbe, the software system for oligonucleotide microarrays using Java. The general criteria for probe design are: (1) probes may have different lengths that range from 20 to 100 bases; (2) they should have a similar melting temperature (Tm) or GC content; (3) they should not contain stable secondary structures; and (4) they abide by Kane's rule.

Computational Biology↗