Non-Local Probes Do Not Help with Graph Problems

This work bridges the gap between distributed and centralised models of computing in the context of sublinear-time graph algorithms. A priori, typical centralised models of computing (e.g., parallel decision trees or centralised local algorithms) seem to be much more powerful than distributed message-passing algorithms: centralised algorithms can directly probe any part of the input, while in distributed algorithms nodes can only communicate with their immediate neighbours. We show that for a large class of graph problems, this extra freedom does not help centralised algorithms at all: for example, efficient stateless deterministic centralised local algorithms can be simulated with efficient distributed message-passing algorithms. In particular, this enables us to transfer existing lower bound results from distributed algorithms to centralised local algorithms

Quantum Geometry and Quantum Gravity

The purpose of this contribution is to give an introduction to quantum geometry and loop quantum gravity for a wide audience of both physicists and mathematicians. From a physical point of view the emphasis will be on conceptual issues concerning the relationship of the formalism with other more traditional approaches inspired in the treatment of the fundamental interactions in the standard model. Mathematically I will pay special attention to functional analytic issues, the construction of the relevant Hilbert spaces and the definition and properties of geometric operators: areas and volumes.Comment: To appear in the AIP Conference Proceedings of the XVI International Fall Workshop on Geometry and Physics, Lisbon - Portugal, 5-8 September 200

Mapping Dynamic Histone Acetylation Patterns to Gene Expression in Nanog-depleted Murine Embryonic Stem Cells

Embryonic stem cells (ESC) have the potential to self-renew indefinitely and to differentiate into any of the three germ layers. The molecular mechanisms for self-renewal, maintenance of pluripotency and lineage specification are poorly understood, but recent results point to a key role for epigenetic mechanisms. In this study, we focus on quantifying the impact of histone 3 acetylation (H3K9,14ac) on gene expression in murine embryonic stem cells. We analyze genome-wide histone acetylation patterns and gene expression profiles measured over the first five days of cell differentiation triggered by silencing Nanog, a key transcription factor in ESC regulation. We explore the temporal and spatial dynamics of histone acetylation data and its correlation with gene expression using supervised and unsupervised statistical models. On a genome-wide scale, changes in acetylation are significantly correlated to changes in mRNA expression and, surprisingly, this coherence increases over time. We quantify the predictive power of histone acetylation for gene expression changes in a balanced cross-validation procedure. In an in-depth study we focus on genes central to the regulatory network of Mouse ESC, including those identified in a recent genome-wide RNAi screen and in the PluriNet, a computationally derived stem cell signature. We find that compared to the rest of the genome, ESC-specific genes show significantly more acetylation signal and a much stronger decrease in acetylation over time, which is often not reflected in an concordant expression change. These results shed light on the complexity of the relationship between histone acetylation and gene expression and are a step forward to dissect the multilayer regulatory mechanisms that determine stem cell fate.Comment: accepted at PLoS Computational Biolog

Locating a robber with multiple probes

We consider a game in which a cop searches for a moving robber on a connected graph using distance probes, which is a slight variation on one introduced by Seager. Carragher, Choi, Delcourt, Erickson and West showed that for any $n$-vertex graph $G$ there is a winning strategy for the cop on the graph $G^{1/m}$ obtained by replacing each edge of $G$ by a path of length $m$, if $m\geq n$. The present authors showed that, for all but a few small values of $n$, this bound may be improved to $m\geq n/2$, which is best possible. In this paper we consider the natural extension in which the cop probes a set of $k$ vertices, rather than a single vertex, at each turn. We consider the relationship between the value of $k$ required to ensure victory on the original graph and the length of subdivisions required to ensure victory with $k=1$. We give an asymptotically best-possible linear bound in one direction, but show that in the other direction no subexponential bound holds. We also give a bound on the value of $k$ for which the cop has a winning strategy on any (possibly infinite) connected graph of maximum degree $\Delta$, which is best possible up to a factor of $(1-o(1))$.Comment: 16 pages, 2 figures. Updated to show that Theorem 2 also applies to infinite graphs. Accepted for publication in Discrete Mathematic

Analysing multiple types of molecular profiles simultaneously: connecting the needles in the haystack

It has been shown that a random-effects framework can be used to test the association between a gene's expression level and the number of DNA copies of a set of genes. This gene-set modelling framework was later applied to find associations between mRNA expression and microRNA expression, by defining the gene sets using target prediction information. Here, we extend the model introduced by Menezes et al (2009) to consider the effect of not just copy number, but also of other molecular profiles such as methylation changes and loss-of-heterozigosity (LOH), on gene expression levels. We will consider again sets of measurements, to improve robustness of results and increase the power to find associations. Our approach can be used genome-wide to find associations, yields a test to help separate true associations from noise and can include confounders. We apply our method to colon and to breast cancer samples, for which genome-wide copy number, methylation and gene expression profiles are available. Our findings include interesting gene expression-regulating mechanisms, which may involve only one of copy number or methylation, or both for the same samples. We even are able to find effects due to different molecular mechanisms in different samples. Our method can equally well be applied to cases where other types of molecular (high-dimensional) data are collected, such as LOH, SNP genotype and microRNA expression data. Computationally efficient, it represents a flexible and powerful tool to study associations between high-dimensional datasets. The method is freely available via the SIM BioConductor package

Algorithmic and Statistical Perspectives on Large-Scale Data Analysis

In recent years, ideas from statistics and scientific computing have begun to interact in increasingly sophisticated and fruitful ways with ideas from computer science and the theory of algorithms to aid in the development of improved worst-case algorithms that are useful for large-scale scientific and Internet data analysis problems. In this chapter, I will describe two recent examples---one having to do with selecting good columns or features from a (DNA Single Nucleotide Polymorphism) data matrix, and the other having to do with selecting good clusters or communities from a data graph (representing a social or information network)---that drew on ideas from both areas and that may serve as a model for exploiting complementary algorithmic and statistical perspectives in order to solve applied large-scale data analysis problems.Comment: 33 pages. To appear in Uwe Naumann and Olaf Schenk, editors, "Combinatorial Scientific Computing," Chapman and Hall/CRC Press, 201