Search PubMed⌕ Search

Biomedical subjects

James J Collins

Publications and source records attributed to James J Collins.

10 recordsLinked to original sources
PubMed2003

Inferring genetic networks and identifying compound mode of action via expression profiling.

The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.

Algorithms↗
PubMed2003

Reverse engineering gene networks: integrating genetic perturbations with dynamical modeling.

While the fundamental building blocks of biology are being tabulated by the various genome projects, microarray technology is setting the stage for the task of deducing the connectivity of large-scale gene networks. We show how the perturbation of carefully chosen genes in a microarray experiment can be used in conjunction with a reverse engineering algorithm to reveal the architecture of an underlying gene regulatory network. Our iterative scheme identifies the network topology by analyzing the steady-state changes in gene expression resulting from the systematic perturbation of a particular node in the network. We highlight the validity of our reverse engineering approach through the successful deduction of the topology of a linear in numero gene network and a recently reported model for the segmentation polarity network in Drosophila melanogaster. Our method may prove useful in identifying and validating specific drug targets and in deconvolving the effects of chemical compounds.

Algorithms↗
PubMed2003

Predicting the dynamic postural control response from quiet-stance behavior in elderly adults.

Human postural sway, as measured by fluctuations of the center of pressure (COP) under the feet of a quietly standing individual, can be characterized as a stochastic process. The fluctuation-dissipation theorem (FDT) provides a linear relationship between the fluctuations of a quasi-static, stochastic system to the same system's relaxation to equilibrium following a perturbation. We applied a similar linear relationship, based on the FDT, to the human postural control system to explore whether anterior-posterior (AP) fluctuations of the COP during quiet stance can be used to predict the AP response of the postural control system to a weak posteriorly directed mechanical perturbation (tug or pull at the waist). We tested 10 healthy elderly (mean age of 69yr) and 10 healthy young (mean age of 25yr) adult subjects. We found that this linear relationship was applicable to the postural control system of all 10 young and eight of the 10 elderly adult subjects. These results suggest that it is possible to predict an individual's dynamic response to a mild perturbation using quiet-stance data, regardless of age. The existence of this FDT-based linear relationship with respect to the human postural control system suggests that, for a given individual, the postural control system may use the same control mechanisms during quiet stance and mild-perturbation conditions, regardless of age.

Adult↗
PubMed2002

Noise-enhanced balance control in older adults.

Somatosensory information is critical to balance control and fall prevention in older adults. Recently, it has been shown that low-level input noise (electrical or mechanical) can enhance the sensitivity of the human somatosensory system. In this study, we tested the effect of low-level electrical noise, applied at the knee, on balance control in 13 healthy elderly volunteers. Subjects performed multiple single-legged stance trials with imperceptible electrical noise applied at the knee during half of the trials. Balance performance was characterized using a force platform to measure the displacement of the center of pressure (COP) under the subject's stance foot. Seven sway parameters were extracted from the COP time series. Improved balance was defined as a reduction in postural sway as indicated by decreases in the COP measures. Six of the seven sway parameters decreased with electrical noise. Three of these parameters decreased significantly ( < 0.05), and a fourth parameter was borderline significant. Averaged across subjects, the application of electrical noise resulted in a 3.8% reduction in mediolateral COP standard deviation ( = 0.04), a 5.4% decrease in the maximum anteroposterior COP excursion ( = 0.03), a 3.1% reduction in the COP path length ( = 0.04), and a 7.8% decrease in swept area ( = 0.05). The results suggest that imperceptible electrical noise, when applied to the knee, can enhance the balance performance of healthy older adults. These findings suggest that electrical noise-based devices may be effective in improving balance control in elderly people.

Aged↗
PubMed2002

Reverse engineering gene networks using singular value decomposition and robust regression.

We propose a scheme to reverse-engineer gene networks on a genome-wide scale using a relatively small amount of gene expression data from microarray experiments. Our method is based on the empirical observation that such networks are typically large and sparse. It uses singular value decomposition to construct a family of candidate solutions and then uses robust regression to identify the solution with the smallest number of connections as the most likely solution. Our algorithm has O(log N) sampling complexity and O(N(4)) computational complexity. We test and validate our approach in a series of in numero experiments on model gene networks.

Algorithms↗
PubMed2002

Enhancing tactile sensation in older adults with electrical noise stimulation.

Older adults often suffer from diminished somatosensation stemming from age-related neuropathy. Recently, localized low-level electrical noise stimulation was shown to enhance tactile sensitivity in healthy young subjects. Here, we hypothesized that fine-touch sensitivity in older adults can be similarly improved. Semmes-Weinstein monofilaments were used to evaluate fine-touch sensitivity on the first metatarsal phalangeal joint with four electrical stimulus conditions and a null (no-noise) condition in nine healthy elderly subjects. Electrical noise stimulation resulted in a statistically significant increase in the number of detections below the null-condition detection threshold, for five of the nine subjects, as well as across the entire population. This work suggests that electrical noise-based techniques may enable people to overcome functional difficulties due to age-related sensory loss.

Aged↗
PubMed2002

Synthetic gene network for entraining and amplifying cellular oscillations.

We present a model for a synthetic gene oscillator and consider the coupling of the oscillator to a periodic process that is intrinsic to the cell. We investigate the synchronization properties of the coupled system, and show how the oscillator can be constructed to yield a significant amplification of cellular oscillations. We reduce the driven oscillator equations to a normal form, and analytically determine the amplification as a function of the strength of the cellular oscillations. The ability to couple naturally occurring genetic oscillations to a synthetically designed network could lead to possible strategies for entraining and/or amplifying oscillations in cellular protein levels.

DNA-Binding Proteins↗
PubMed2002

Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. DESIGN: A randomized controlled study. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE: Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.

Adult↗