Showing papers by "Michael Q. Zhang published in 1998"

Comprehensive Identification of Cell Cycle–regulated Genes of the Yeast Saccharomyces cerevisiae by Microarray Hybridization

Abstract: We sought to create a comprehensive catalog of yeast genes whose transcript levels vary periodically within the cell cycle. To this end, we used DNA microarrays and samples from yeast cultures sync...

Identification of functional exonic splicing enhancer motifs recognized by individual SR proteins

Abstract: Using an in vitro randomization and functional selection procedure, we have identified three novel classes of exonic splicing enhancers (ESEs) recognized by human SF2/ASF, SRp40, and SRp55, respectively. These ESEs are functional in splicing and are highly specific. For SF2/ASF and SRp55, in most cases, only the cognate SR protein can efficiently recognize an ESE and activate splicing. In contrast, the SRp40-selected ESEs can function with either SRp40 or SRp55, but not with SF2/ASF. UV cross-linking/competition and immunoprecipitation experiments showed that SR proteins recognize their cognate ESEs in nuclear extract by direct and specific binding. A motif search algorithm was used to derive consensus sequences for ESEs recognized by these SR proteins. Each SR protein yielded a distinct 5- to 7-nucleotide degenerate consensus. These three consensus sequences occur at higher frequencies in exons than in introns and may thus help define exon–intron boundaries. They occur in clusters within regions corresponding to naturally occurring, mapped ESEs. We conclude that a remarkably diverse set of sequences can function as ESEs. The degeneracy of these motifs is consistent with the fact that exonic enhancers evolved within extremely diverse protein coding sequences and are recognized by a small number of SR proteins that bind RNA with limited sequence specificity.

Statistical Features of Human Exons and Their Flanking Regions

Abstract: To facilitate gene finding and for the investigation of human molecular genetics on a genome scale, we present a comprehensive survey on various statistical features of human exons. We first show that human exons with flanking genomic DNA sequences can be classified into 12 mutually exclusive categories. This classification could serve as a standard for future studies so that direct comparisons of results can be made. A database for eight categories (related to human genes in which coding regions are split by introns) was built from GenBank release 87.0 and analyzed by a number of methods to characterize statistical features of these sequences that may serve as controls or regulatory signals for gene expression. The statistical information compiled includes profiles of signals for transcription, splicing and translation, various compositional statistics and size distributions. Further analyses reveal novel correlations and constraints among different splicing features across an internal exon that are consistent with the Exon Definition model. This information is fundamental for a quantitative view of human gene organization, and should be invaluable for individual scientists to design human molecular genetics experiments.

Identification of Human Gene Core Promoters in Silico

Abstract: Identification of the 58-end of human genes requires identification of functional promoter elements. In silico identification of those elements is difficult because of the hierarchical and modular nature of promoter architecture. To address this problem, I propose a new stepwise strategy based on initial localization of a functional promoter into a 1- to 2-kb (extended promoter) region from within a large genomic DNA sequence of 100 kb or larger and further localization of a transcriptional start site (TSS) into a 50- to 100-bp (corepromoter) region. Using positional dependent 5-tuple measures, a quadratic discriminant analysis (QDA) method has been implemented in a new program—CorePromoter. Our experiments indicate that when given a 1- to 2-kb extended promoter, CorePromoter will correctly localize the TSS to a 100-bp interval ~60% of the time. [Figure 3 can be found in its entirety as an online supplement at http://www.genome.org.] As the Human Genome Project enters its large-scale sequencing phase, methods for the identification of genes and regulatory elements in silico have become extremely important (Business Week 1996).

A discrimination study of human core-promoters.

Abstract: A core-promoter, approximately from -60 bp upstream to +40 bp downstream of a RNA polymerase (RNAP) II transcription start site (TSS), binds to the preinitiation complex (PIC) and determine the position of TSS. Using position-specific k-tuple feature variables, a quadratic discriminant analysis (QDA) method is shown to be very effective in identifying human core-promoters.

Pombe: A gene-finding and exon-intron structure prediction system for fission yeast

Abstract: A special program developed by the authors, called Pombe, identifies protein coding regions in the Schizosaccharomyces pombe genome Linear discriminant analysis was applied to predict 5*-terminal, internal, 3*-terminal exons (coding-exon) and introns The accuracy of the prediction was tested by cross verifications The sensitivity, specificity and correlation coeYcient for the internal exon prediction were 98·5%, 99·9% and 98·3% respectively at the nucleotide level Open reading frames were studied and used to predict intron-less genes: 99·0% of such genes were identified with correct stopping sites The gene structure was determined by dynamic programming and the prediction achieved 97·0% correlation coeYcient at the nucleotide level The program is available at http://cliocshlorg/genefinder ? 1998 John Wiley & Sons, Ltd

Identification of protein-coding regions in Arabidopsis thaliana genome based on quadratic discriminant analysis

Abstract: A new method (MZEF) for predicting internal coding exons in genomic DNA sequences has been developed. This method is based on a prediction algorithm that uses the quadratic discriminant function for multivariate statistical pattern recognition. With improved feature measures, an Arabidopsis thaliana-specific implementation of MZEF is completed and made available to the plant genome community.