Biomedical subjects

T Ideker

Publications and source records attributed to T Ideker.

5 recordsLinked to original sources

PubMed2001

Integrated genomic and proteomic analyses of a systematically perturbed metabolic network.

We demonstrate an integrated approach to build, test, and refine a model of a cellular pathway, in which perturbations to critical pathway components are analyzed using DNA microarrays, quantitative proteomics, and databases of known physical interactions. Using this approach, we identify 997 messenger RNAs responding to 20 systematic perturbations of the yeast galactose-utilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physical interactions governing the cellular response to each perturbation. We refine the model through further iterations of perturbation and global measurements, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pathways.

Computational Biology↗

PubMed2001

A new approach to decoding life: systems biology.

Systems biology studies biological systems by systematically perturbing them (biologically, genetically, or chemically); monitoring the gene, protein, and informational pathway responses; integrating these data; and ultimately, formulating mathematical models that describe the structure of the system and its response to individual perturbations. The emergence of systems biology is described, as are several examples of specific systems approaches.

Animals↗

PubMed2000

Testing for differentially-expressed genes by maximum-likelihood analysis of microarray data.

Although two-color fluorescent DNA microarrays are now standard equipment in many molecular biology laboratories, methods for identifying differentially expressed genes in microarray data are still evolving. Here, we report a refined test for differentially expressed genes which does not rely on gene expression ratios but directly compares a series of repeated measurements of the two dye intensities for each gene. This test uses a statistical model to describe multiplicative and additive errors influencing an array experiment, where model parameters are estimated from observed intensities for all genes using the method of maximum likelihood. A generalized likelihood ratio test is performed for each gene to determine whether, under the model, these intensities are significantly different. We use this method to identify significant differences in gene expression among yeast cells growing in galactose-stimulating versus non-stimulating conditions and compare our results with current approaches for identifying differentially-expressed genes. The effect of sample size on parameter optimization is also explored, as is the use of the error model to compare the within- and between-slide intensity variation intrinsic to an array experiment.

Galactose↗

PubMed1999

Negative selection: a method for obtaining low-abundance cDNAs using high-density cDNA clone arrays.

The identification of the entire complement of genes expressed in a cell, tissue, or organism provides a framework for understanding biological properties and establishes a tool set for subsequent functional studies. The large-scale sequencing of randomly selected clones from cDNA libraries has been successfully employed as a method for identifying a large fraction of these expressed genes. However, this approach is limited by the inherent redundancy of cellular transcripts reflecting widely variant levels of gene transcription. As a result, a high percentage of transcript duplications are encountered as the number of sequenced clones accrues. To address this problem, we have developed a negative hybridization selection method that employs the hybridization of complex cDNA probes to high-density arrays of cDNA clones and the subsequent selection of clones with a null or low hybridization signal. This approach was applied to a cDNA library constructed from normal human prostate tissue and resulted in the reduction of highly expressed prostate cDNAs from 6.8 to 0.57% with an overall decline in clone redundancy from 33 to 11%. The selected clones also reflected a more diverse cDNA population, with 89% of the clones representing distinctly different cDNAs compared with 67% of the randomly selected clones. This method compares favorably with cDNA library re-association normalization approaches and offers several distinct advantages, including the flexibility to use previously prepared libraries, and the ability to employ an iterative screening approach for continued accrual of cDNAs representing rare transcripts.

DNA, Complementary↗

PubMed1997

Effect of electrode position on outcome of low-energy intracardiac cardioversion of atrial fibrillation.

The aim of this study was to evaluate the new method of low-energy, catheter-based intracardiac cardioversion in patients with chronic atrial fibrillation (AF) and to compare 2 different lead positions. Accordingly, we prospectively studied 80 consecutive patients with chronic AF (9.8 +/- 7.9 months) who were randomly assigned to undergo internal cardioversion either via defibrillation electrodes placed in the right atrium and coronary sinus (coronary sinus group) or via defibrillation electrodes placed in the right atrium and left pulmonary artery (pulmonary artery group). Intracardiac shocks were delivered by an external defibrillator synchronized to the QRS complex. After conversion, all patients were treated orally with sotalol (mean daily dose, 189 +/- 63 mg/day). For conversion to sinus rhythm, the overall mean energy requirement was 5.6 +/- 3.1 J. In the coronary sinus group, cardioversion was achieved in 35 of 38 patients at a mean energy level of 4.1 +/- 2.3 J (range 1.0 to 9.9), and in the pulmonary artery group in 39 of 42 patients with 7.2 +/- 3.1 J (range 2.5 to 14.8). Although there was no difference with regard to success rate, the energy differed significantly between the 2 groups (p < 0.01). Mean lead impedance was 56.4 +/- 7.0 omega and 54.6 +/- 8.5 omega, respectively (p = NS). No serious complications were observed in either lead group. At a mean follow-up of 14.2 +/- 7.0 months, 54% and 56%, respectively, of patients who had been converted successfully remained in sinus rhythm. Thus, low-energy biphasic shocks delivered between the right atrium and coronary sinus or pulmonary artery are equally effective for cardioversion of patients with chronic AF. The energy requirements for conversion from a pulmonary artery electrode position are higher than for the coronary sinus position.

Administration, Oral↗