A Database Designed to Computationally Aid an Experimental Approach to Alternative Splicing

Cl, Zheng; Nair, T. Murlidharan; Gribskov, Michael; Kwon, Yong Soo; Li, HR; Xd, Fu

doi:10.1142/9789812704856_0008

Cited by 11 publications

(6 citation statements)

References 23 publications

(17 reference statements)

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“…Data sets were retrieved from the Manually Annotated Alternatively Spliced Events (MAASE) Database (Zheng et al 2004;Zheng et al 2005). We use the following nomenclature and abbreviations for different splicing modes and their associated intron sequences.…”

Section: Data Setmentioning

confidence: 99%

“…Although several alternative splicing database efforts considered different modes of splicing, those analyses suffered from either limited database content or insufficient quality control on the computationally derived information. We have constructed the MAASE database system to support our splicing microarray efforts (Zheng et al 2004). The MAASE database system consists of a manual/ computational tool for annotating alternative splicing events and a database of highly curated information annotated.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

Zheng

Fu²,

Gribskov³

2005

RNA

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Alternative splicing is a major contributor to genomic complexity, disease, and development. Previous studies have captured some of the characteristics that distinguish alternative splicing from constitutive splicing. However, most published work only focuses on skipped exons and/or a single species. Here we take advantage of the highly curated data in the MAASE database (see related paper in this issue) to analyze features that characterize different modes of splicing. Our analysis confirms previous observations about alternative splicing, including weaker splicing signals at alternative splice sites, higher sequence conservation surrounding orthologous alternative exons, shorter exon length, and more frequent reading frame maintenance in skipped exons. In addition, our study reveals potentially novel regulatory principles underlying distinct modes of alternative splicing and a role of a specific class of repeat elements (transposons) in the origin/evolution of alternative exons. These features suggest diverse regulatory mechanisms and evolutionary paths for different modes of alternative splicing.

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Section: Data Setmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

Zheng

Fu²,

Gribskov³

2005

RNA

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“…Several genes have been shown to produce both [85] soluble and membrane-associated protein isoforms by selective incorporation of exons encoding transmembrane regions. In particular, several tumor necrosis factor receptor (TNFR) genes are alternatively spliced in a regulated manner to produce either soluble or membrane-associated signal-transducing forms [10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

The evolving roles of alternative splicing

Lareau

Green

Bhatnagar

et al. 2004

Current Opinion in Structural Biology

283

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Alternative splicing is now commonly thought to affect more than half of all human genes. Recent studies have investigated not only the scope but also the biological impact of alternative splicing on a large scale, revealing that its role in generating proteome diversity may be augmented by a role in regulation. For instance, protein function can be regulated by the removal of interaction or localization domains by alternative splicing. Alternative splicing can also regulate gene expression by splicing transcripts into unproductive mRNAs targeted for degradation. To fully understand the scope of alternative splicing, we must also determine how many of the predicted splice variants represent functional forms. Comparisons of alternative splicing between human and mouse genes show that predominant splice variants are usually conserved, but rare variants are less commonly shared. Evolutionary conservation of splicing patterns suggests functional importance and provides insight into the evolutionary history of alternative splicing. The definition of functional splicing has evolved to match our increased understanding of gene expression.At the same time that we realized the human genome has far fewer genes than expected, we began to appreciate the full extent of alternative splicing. Many concluded that alternative splicing led to proteome expansion, bridging a perceived complexity gap. However, complexity is not determined simply by proteome size; it also encompasses interactions and regulation. Recently, we have begun to better understand alternative splicing as a regulatory process, contributing to biological complexity through its ability to control the expression of proteins. A recent paper provides a modern definition of functional splicing: ''An mRNA variant can be defined as being 'functional' if it is required during the life-cycle of the organism and activated in a regulated manner'' [2 ]. In some cases, functional splice forms may not even be required in their own right, but their production is required to regulate active protein levels. Moreover, the meaning of 'required' can be generalized by defining functional splicing as that which conveys a selective advantage.Well before alternative splicing was known to be widespread, studies showed that control of splicing could act as a general on/off switch to regulate gene expression [3]. Work on mRNA stability in Caenorhabditis elegans indicated that alternative splicing of serine/argininerich (SR) proteins, themselves involved in alternative splicing, could regulate their expression [4]. Recently, the combination of large-scale studies, enabled by the large data sets now available (Table 1), and studies of individual alternatively spliced genes has shed light on the regulatory roles and evolution of alternative splicing.Large-scale studies of the regulatory impact of alternative splicingThe first large-scale studies of alternative splicing were inventory-style analyses, designed to determine the extent of alternative splicing. The results of those surveys, tha...

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“…Due to the limitations of the existing databases, we have built the Manually Annotated Alternatively Spliced Events (MAASE) database system with experimentalists and splicing array platforms explicitly in mind (Zheng et al 2004). Our goal is to provide a comprehensive tool for annotating and organizing sequence and functional information relevant to alternative splicing.…”

Section: Introductionmentioning

confidence: 99%

MAASE: An alternative splicing database designed for supporting splicing microarray applications

Zheng

Kwon²,

Li³

et al. 2005

RNA

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Alternative splicing is a prominent feature of higher eukaryotes. Understanding of the function of mRNA isoforms and the regulation of alternative splicing is a major challenge in the post-genomic era. The development of mRNA isoform sensitive microarrays, which requires precise splice-junction sequence information, is a promising approach. Despite the availability of a large number of mRNAs and ESTs in various databases and the efforts made to align transcript sequences to genomic sequences, existing alternative splicing databases do not offer adequate information in an appropriate format to aid in splicing array design. Here we describe our effort in constructing the Manually Annotated Alternatively Spliced Events (MAASE) database system, which is specifically designed to support splicing microarray applications. MAASE comprises two components: (1) a manual/ computational annotation tool for the efficient extraction of critical sequence and functional information for alternative splicing events and (2) a user-friendly database of annotated events that allows convenient export of information to aid in microarray design and data analysis. We provide a detailed introduction and a step-by-step user guide to the MAASE database system to facilitate future large-scale annotation efforts, integration with other alternative splicing databases, and splicing array fabrication.

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A Database Designed to Computationally Aid an Experimental Approach to Alternative Splicing

Cited by 11 publications

References 23 publications

Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

Characteristics and regulatory elements defining constitutive splicing and different modes of alternative splicing in human and mouse

The evolving roles of alternative splicing

MAASE: An alternative splicing database designed for supporting splicing microarray applications

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