6 results on '"Mark A. Ragan"'
Search Results
2. Characterizing cancer subtypes as attractors of Hopfield networks
- Author
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Mark A. Ragan and Stefan Maetschke
- Subjects
Statistics and Probability ,Computer science ,Gene regulatory network ,Inference ,Feature selection ,computer.software_genre ,Biochemistry ,Hopfield network ,Neoplasms ,Attractor ,Feature (machine learning) ,Cluster Analysis ,Humans ,Gene Regulatory Networks ,Pruning (decision trees) ,Cluster analysis ,Molecular Biology ,Gene Expression Profiling ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Kinetics ,Computational Mathematics ,Computational Theory and Mathematics ,Data mining ,computer ,Algorithms ,Software - Abstract
Motivation: Cancer is a heterogeneous progressive disease caused by perturbations of the underlying gene regulatory network that can be described by dynamic models. These dynamics are commonly modeled as Boolean networks or as ordinary differential equations. Their inference from data is computationally challenging, and at least partial knowledge of the regulatory network and its kinetic parameters is usually required to construct predictive models. Results: Here, we construct Hopfield networks from static gene-expression data and demonstrate that cancer subtypes can be characterized by different attractors of the Hopfield network. We evaluate the clustering performance of the network and find that it is comparable with traditional methods but offers additional advantages including a dynamic model of the energy landscape and a unification of clustering, feature selection and network inference. We visualize the Hopfield attractor landscape and propose a pruning method to generate sparse networks for feature selection and improved understanding of feature relationships. Availability: Software and datasets are available at http://acb.qfab.org/acb/hclust/ Contact: m.ragan@uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
- Published
- 2014
- Full Text
- View/download PDF
3. A word-oriented approach to alignment validation
- Author
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Cheong Xin Chan, Robert G. Beiko, and Mark A. Ragan
- Subjects
Statistics and Probability ,Protein family ,Sequence analysis ,Sequence alignment ,Biology ,computer.software_genre ,Biochemistry ,Pattern Recognition, Automated ,Artificial Intelligence ,Sequence Analysis, Protein ,Molecular Biology ,Natural Language Processing ,Multiple sequence alignment ,business.industry ,Proteins ,Automation ,Semantics ,Computer Science Applications ,Computational Mathematics ,Validation methods ,Computational Theory and Mathematics ,Positive relationship ,Data mining ,Artificial intelligence ,Optimal alignment ,business ,Sequence Alignment ,computer ,Algorithms ,Natural language processing - Abstract
Motivation: Multiple sequence alignment at the level of whole proteomes requires a high degree of automation, precluding the use of traditional validation methods such as manual curation. Since evolutionary models are too general to describe the history of each residue in a protein family, there is no single algorithm/model combination that can yield a biologically or evolutionarily optimal alignment. We propose a 'shotgun' strategy where many different algorithms are used to align the same family, and the best of these alignments is then chosen with a reliable objective function. We present WOOF, a novel 'word-oriented' objective function that relies on the identification and scoring of conserved amino acid patterns (words) between pairs of sequences. Results: Tests on a subset of reference protein alignments from BAliBASE showed that WOOF tended to rank the (manually curated) reference alignment highest among 1060 alternative (automatically generated) alignments for a majority of protein families. Among the automated alignments, there was a strong positive relationship between the WOOF score and similarity to the reference alignment. The speed of WOOF and its independence from explicit considerations of three-dimensional structure make it an excellent tool for analyzing large numbers of protein families. Availability: On request from the authors. Contact: m.ragan@imb.uq.edu.au
- Published
- 2005
- Full Text
- View/download PDF
4. Illoura™: a software tool for analysis, visualization and semantic querying of cellular and other spatial biological data
- Author
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Tim McComb, Oliver Cairncross, Brad J. Marsh, Andrew B. Noske, David L. A. Wood, and Mark A. Ragan
- Subjects
Statistics and Probability ,Databases, Factual ,Computer science ,Cells ,Semantic analysis (machine learning) ,Information Storage and Retrieval ,computer.software_genre ,Semantics ,Biochemistry ,Computer graphics ,Software ,Computer Graphics ,Molecular Biology ,Spatial analysis ,Biological data ,business.industry ,Computational Biology ,Computer Science Applications ,Visualization ,Applications Note ,Computational Mathematics ,Computational Theory and Mathematics ,Data mining ,business ,computer - Abstract
Summary: New high-resolution approaches for mapping ultrastructure of cells in 3D are leading to unprecedented quantities of spatial data. Here we present Illoura, a software tool for the integrated management, analysis and visualization of these data within a semantic context, and illustrate its capability by analysis of spatial relationships in mammalian beta cells. Availability: http://www.visiblecell.com/illoura Contact: m.ragan@uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
- Published
- 2009
- Full Text
- View/download PDF
5. A word-oriented approach to alignment validation.
- Author
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Mark A. Ragan
- Published
- 2005
6. MACHOS: Markov clusters of homologous subsequences.
- Author
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Simon Wong and Mark A. Ragan
- Subjects
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PROTEINS , *AMINO acid sequence , *BIOMOLECULES , *SEQUENCE spaces - Abstract
Motivation: The classification of proteins into homologous groups (families) allows their structure and function to be analysed and compared in an evolutionary context. The modular nature of eukaryotic proteins presents a considerable challenge to the delineation of families, as different local regions within a single protein may share common ancestry with distinct, even mutually exclusive, sets of homologs, thereby creating an intricate web of homologous relationships if full-length sequences are taken as the unit of evolution. We attempt to disentangle this web by developing a fully automated pipeline to delineate protein subsequences that represent sensible units for homology inference, and clustering them into putatively homologous families using the Markov clustering algorithm. Results: Using six eukaryotic proteomes as input, we clustered 162 349 protein sequences into 19 697–77 415 subsequence families depending on granularity of clustering. We validated these Markov clusters of homologous subsequences (MACHOS) against the manually curated Pfam domain families, using a quality measure to assess overlap. Our subsequence families correspond well to known domain families and achieve higher quality scores than do groups generated by fully automated domain family classification methods. We illustrate our approach by analysis of a group of proteins that contains the glutamyl/glutaminyl-tRNA synthetase domain, and conclude that our method can produce high-coverage decomposition of protein sequence space into precise homologous families in a way that takes the modularity of eukaryotic proteins into account. This approach allows for a fine-scale examination of evolutionary histories of proteins encoded in eukaryotic genomes. Contact: m.ragan@imb.uq.edu.au Supplementary information: Supplementary data are available at Bioinformatics online. MACHOS for the six proteomes are available as FASTA-formatted files: http://research1t.imb.uq.edu.au/ragan/machos [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
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