Finding regulatory modules through large-scale gene-expression data analysis

The use of gene microchips has enabled a rapid accumulation of gene-expression data. One of the major challenges of analyzing this data is the diversity, in both size and signal strength, of the various modules in the gene regulatory networks of organisms. Based on the Iterative Signature Algorithm [Bergmann, S., Ihmels, J. and Barkai, N. (2002) Phys. Rev. E 67, 031902], we present an algorithm - the Progressive Iterative Signature Algorithm (PISA) - that, by sequentially eliminating modules, allows unsupervised identification of both large and small regulatory modules. We applied PISA to a large set of yeast gene-expression data, and, using the Gene Ontology annotation database as a reference, found that our algorithm is much better able to identify regulatory modules than methods based on high-throughput transcription-factor binding experiments or on comparative genomics.Comment: 7 pages, 6 figures in main text; 2 text pages, 7 figures, 1 table in supplement; rewritten versio

Modeling Evolution of Crosstalk in Noisy Signal Transduction Networks

Signal transduction networks can form highly interconnected systems within cells due to network crosstalk, the sharing of input signals between multiple downstream responses. To better understand the evolutionary design principles underlying such networks, we study the evolution of crosstalk and the emergence of specificity for two parallel signaling pathways that arise via gene duplication and are subsequently allowed to diverge. We focus on a sequence based evolutionary algorithm and evolve the network based on two physically motivated fitness functions related to information transmission. Surprisingly, we find that the two fitness functions lead to very different evolutionary outcomes, one with a high degree of crosstalk and the other without.Comment: 18 Pages, 16 Figure

Phase measurement of photon-assisted tunneling through a quantum dot

Recent double-slit interference experiments have demonstrated the possibility of probing the phase of the complex transmission coefficient of a quantum dot via the Aharonov-Bohm effect. We propose an extension of these experiments: an ac voltage imposed on the side gate with the concomitant photonic sidebands leads to additional structure both in the amplitude and in the phase of the Aharonov-Bohm signal. Observation of these effects would be a definitive proof of coherent absorption and reemission of photons from the ac source.Comment: 6 pages using latex2e and EuroPhys.sty. Uses epsf to include 5 figures (submitted to Europhys. Lett.

Quantum-Dot Cascade Laser: Proposal for an Ultra-Low-Threshold Semiconductor Laser

We propose a quantum-dot version of the quantum-well cascade laser of Faist et al. [Science {\bf 264}, 553 (1994)]. The elimination of single phonon decays by the three-dimensional confinement implies a several order-of-magnitude reduction in the threshold current. The requirements on dot size (10-20nm) and on dot density and uniformity [one coupled pair of dots per (180nm)^3 with 5% nonuniformity] are close to current technology.Comment: 8 pages, REVTEX 3.0, 3 compressed postscript figure

Exponential sensitivity of noise-driven switching in genetic networks

Cells are known to utilize biochemical noise to probabilistically switch between distinct gene expression states. We demonstrate that such noise-driven switching is dominated by tails of probability distributions and is therefore exponentially sensitive to changes in physiological parameters such as transcription and translation rates. However, provided mRNA lifetimes are short, switching can still be accurately simulated using protein-only models of gene expression. Exponential sensitivity limits the robustness of noise-driven switching, suggesting cells may use other mechanisms in order to switch reliably