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Ma, T.

Publications and source records attributed to Ma, T..

4 recordsLinked to original sources

Comparative Pathway Integrator: a framework of meta-analytic integration of multiple transcriptomic studies for consensual and differential pathway analysis

MotivationPathway analysis provides a knowledge-driven approach to interpret differentially expressed genes associated with disease status. Many tools have been developed to analyze a single study. When multiple studies of different conditions are jointly analyzed, novel integrative tools are needed. In addition, pathway redundancy issue introduced by combining public pathway databases hinders knowledge discovery.\n\nMethods and ResultsWe present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fishers method to discover consensual and differential enrichment patterns, consensus clustering to reduce pathway redundancy, and a novel text mining algorithm to assist interpretation of the pathway clusters. We applied CPI to jointly analyze six psychiatric disorder transcriptomic studies to demonstrate its effectiveness, and found functions confirmed by previous biological studies as well novel enrichment patterns.\n\nAvailabilityCPI is accessible online: http://tsenglab.biostat.pitt.edu/software.htm.\n\nContactxiangruz@andrew.cmu.edu

bioinformatics

Substantia nigra dopamine neurons evoke a delayed excitation in lateral dorsal striatal cholinergic interneurons via glutamate cotransmission

Dopamine neurons have different synaptic actions in the ventral and dorsal striatum (dStr), but whether this heterogeneity extends to dStr subregions has not been addressed. We have found that optogenetic activation of dStr dopamine neuron terminals in mouse brain slices pauses the firing of cholinergic interneurons in both the medial and lateral subregions, while in the lateral subregion the pause is shorter due to a subsequent excitation. This excitation is mediated mainly by metabotropic glutamate receptor 1 (mGluR1) and partially by dopamine D1-like receptors coupled to transient receptor potential channel 3 and 7. DA neurons do not signal to spiny projection neurons in the medial dStr, while they elicit ionotropic glutamate responses in the lateral dStr. The DA neurons mediating these excitatory signals are in the substantia nigra (SN). Thus, SN dopamine neurons engage different receptors in different postsynaptic neurons in different dStr subregions to convey strikingly different signals.

neuroscience

OPUS-CSF: A C-atom-based Scoring Function for Ranking Protein Structural Models

We report a C-atom-based scoring function, named OPUS-CSF, for ranking protein structural models. Rather than using traditional Boltzmann formula, we built a scoring function (CSF score) based on the native distributions (analyzed through entire PDB) of coordinate components of mainchain C atoms on selected residues of peptide segments of 5, 7, 9, and 11 residues in length. In testing OPUS-CSF on decoy recognition, it maximally recognized 257 native structures out of 278 targets in 11 commonly used decoy sets, significantly more than other popular all-atom empirical potentials. The average correlation coefficient with TM-score was also comparable with those of other potentials. OPUS-CSF is a highly coarse-grained scoring function, which only requires input of partial mainchain information, and very fast. Thus it is suitable for applications at early stage of structural building.

biophysics

CircularLogo: A light weighted web application to visualize intra-motif dependencies

BackgroundThe sequence logo has been widely used to represent DNA or RNA motifs for more than three decades. Despite its intelligibility and intuitiveness, the traditional sequence logo is unable to display the intra-motif dependencies and therefore is insufficient to fully characterize nucleotide motifs. Many methods have been developed to quantify the intra-motif dependencies, but fewer tools are available for visualization.\n\nResultWe developed CircularLogo, a web-based interactive application, which is able to not only visualize the position-specific nucleotide consensus and diversity but also display the intra-motif dependencies. Applying CircularLogo to HNF6 binding sites and tRNA sequences demonstrated its ability to show intra-motif dependencies and intuitively reveal biomolecular structure. CircularLogo is implemented in JavaScript and Python based on the Django web framework. The programs source code and users manual are freely available at http://circularlogo.sourceforge.net. CircularLogo web server can be accessed from http://bioinformaticstools.mayo.edu/circularlogo/index.html.\n\nConclusionCircularLogo is an innovative web application that is specifically designed to visualize and interactively explore intra-motif dependencies.

bioinformatics