Biomedical subjects

Tuan D Pham

Publications and source records attributed to Tuan D Pham.

4 recordsLinked to original sources

PubMed2006

LPC cepstral distortion measure for protein sequence comparison.

Protein sequence comparison is the most powerful tool for the inference of novel protein structure and function. This type of inference is commonly based on the similar sequence-similar structure-similar function paradigm, and derived by sequence similarity searching on databases of protein sequences. As entire genomes have been being determined at a rapid rate, computational methods for comparing protein sequences will be more essential for probing the complexity of molecular machines. In this paper we introduce a pattern-comparison algorithm, which is based on the mathematical concepts of linear predictive coding (LPC) and LPC cepstral distortion measure, for computing similarities/dissimilarities between protein sequences. Experimental results on a real data set of functionally related and functionally nonrelated protein sequences have shown the effectiveness of the proposed approach on both accuracy and computational efficiency.

Algorithms↗

PubMed2004

A probabilistic measure for alignment-free sequence comparison.

MOTIVATION: Alignment-free sequence comparison methods are still in the early stages of development compared to those of alignment-based sequence analysis. In this paper, we introduce a probabilistic measure of similarity between two biological sequences without alignment. The method is based on the concept of comparing the similarity/dissimilarity between two constructed Markov models. RESULTS: The method was tested against six DNA sequences, which are the thrA, thrB and thrC genes of the threonine operons from Escherichia coli K-12 and from Shigella flexneri; and one random sequence having the same base composition as thrA from E.coli. These results were compared with those obtained from CLUSTAL W algorithm (alignment-based) and the chaos game representation (alignment-free). The method was further tested against a more complex set of 40 DNA sequences and compared with other existing sequence similarity measures (alignment-free). AVAILABILITY: All datasets and computer codes written in MATLAB are available upon request from the first author.

Algorithms↗

PubMed2004

Bone morphogenetic protein-2 and -4 limit the number of enteric neurons but promote development of a TrkC-expressing neurotrophin-3-dependent subset.

The hypothesis that BMPs (bone morphogenetic proteins), which act early in gut morphogenesis, also regulate specification and differentiation in the developing enteric nervous system (ENS) was tested. Expression of BMP-2 and BMP-4, BMPR-IA (BMP receptor subunit), BMPR-IB, and BMPR-II, and the BMP antagonists, noggin, gremlin, chordin, and follistatin was found when neurons first appear in the primordial bowel at embryonic day 12 (E12). Agonists, receptors, and antagonists were detected in separated populations of neural crest- and noncrest-derived cells. When applied to immunopurified E12 ENS precursors, BMP-2 and BMP-4 induced nuclear translocation of phosphorylated Smad-1 (Sma and Mad-related protein). The number of neurons developing from these cells was increased by low concentrations and decreased by high concentrations of BMP-2 or BMP-4. BMPs induced the precocious appearance of TrkC-expressing neurons and their dependence on neurotrophin-3 for survival. BMP-4 interacted with glial cell line-derived neurotrophic factor (GDNF) to enhance neuronal development but limited GDNF-driven expansion of the precursor pool. BMPs also promoted development of smooth muscle from mesenchymal cells immunopurified at E12. To determine the physiological significance of these observations, the BMP antagonist noggin was overexpressed in the developing ENS of transgenic mice under the control of the neuron-specific enolase promoter. Neuronal numbers in both enteric plexuses and smooth muscle were increased throughout the postnatal small intestine. These increases were already apparent by E18. In contrast, TrkC-expressing neurons decreased in both plexuses of postnatal noggin-overexpressing animals, again an effect detectable at E18. BMP-2 and/or BMP-4 thus limit the size of the ENS but promote the development of specific subsets of enteric neurons, including those that express TrkC.

Active Transport, Cell Nucleus↗

PubMed2004

Extraction of fluorescent cell puncta by adaptive fuzzy segmentation.

MOTIVATION: The discrimination and measurement of fluorescent-labeled vesicles using microscopic analysis of fixed cells presents a challenge for biologists interested in quantifying the abundance, size and distribution of such vesicles in normal and abnormal cellular situations. In the specific application reported here, we were interested in quantifying changes to the population of a major organelle, the peroxisome, in cells from normal control patients and from patients with a defect in peroxisome biogenesis. In the latter, peroxisomes are present as larger vesicular structures with a more restricted cytoplasmic distribution. Existing image processing methods for extracting fluorescent cell puncta do not provide useful results and therefore, there is a need to develop some new approaches for dealing with such a task effectively. RESULTS: We present an effective implementation of the fuzzy c-means algorithm for extracting puncta (spots), representing fluorescent-labeled peroxisomes, which are subject to low contrast. We make use of the quadtree partition to enhance the fuzzy c-means based segmentation and to disregard regions which contain no target objects (peroxisomes) in order to minimize considerable time taken by the iterative process of the fuzzy c-means algorithm. We finally isolate touching peroxisomes by an aspect-ratio criterion. The proposed approach has been applied to extract peroxisomes contained in several sets of color images and the results are superior to those obtained from a number of standard techniques for spot extraction. AVAILABILITY: Image data and computer codes written in Matlab are available upon request from the first author.

Algorithms↗