Iterative Random Forests to detect predictive and stable high-order interactions

Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order interactions drive gene expression presents a substantial statistical challenge. Building on Random Forests (RF), Random Intersection Trees (RITs), and through extensive, biologically inspired simulations, we developed the iterative Random Forest algorithm (iRF). iRF trains a feature-weighted ensemble of decision trees to detect stable, high-order interactions with same order of computational cost as RF. We demonstrate the utility of iRF for high-order interaction discovery in two prediction problems: enhancer activity in the early Drosophila embryo and alternative splicing of primary transcripts in human derived cell lines. In Drosophila, among the 20 pairwise transcription factor interactions iRF identifies as stable (returned in more than half of bootstrap replicates), 80% have been previously reported as physical interactions. Moreover, novel third-order interactions, e.g. between Zelda (Zld), Giant (Gt), and Twist (Twi), suggest high-order relationships that are candidates for follow-up experiments. In human-derived cells, iRF re-discovered a central role of H3K36me3 in chromatin-mediated splicing regulation, and identified novel 5th and 6th order interactions, indicative of multi-valent nucleosomes with specific roles in splicing regulation. By decoupling the order of interactions from the computational cost of identification, iRF opens new avenues of inquiry into the molecular mechanisms underlying genome biology

A reversible infinite HMM using normalised random measures

We present a nonparametric prior over reversible Markov chains. We use completely random measures, specifically gamma processes, to construct a countably infinite graph with weighted edges. By enforcing symmetry to make the edges undirected we define a prior over random walks on graphs that results in a reversible Markov chain. The resulting prior over infinite transition matrices is closely related to the hierarchical Dirichlet process but enforces reversibility. A reinforcement scheme has recently been proposed with similar properties, but the de Finetti measure is not well characterised. We take the alternative approach of explicitly constructing the mixing measure, which allows more straightforward and efficient inference at the cost of no longer having a closed form predictive distribution. We use our process to construct a reversible infinite HMM which we apply to two real datasets, one from epigenomics and one ion channel recording.Comment: 9 pages, 6 figure

Adaptive Network on Chip Routing using the Turn Model

To create a viable network on chip, many technical challenges need to be solved. One of the aspects of solutions is the routing algorithm: how to route packets from one component (e.g., core CPU) to another without deadlock or livelock while avoiding congestion or faulty routers. Routing algorithms must deal with these problems while remaining simple enough to keep the hardware cost low. We have created a simple to implement, deadlock free, and livelock free routing algorithm that addresses these challenges. This routing algorithm, Weighted Non-Minimal OddEven (WeNMOE), gathers information on the state of the network (congestion/faults) from surrounding routers. The algorithm then uses this information to estimate a routing cost and routes down the path with the lowest estimated cost. A simulator was developed and used to study the performance and to compare the new routing algorithm against other state of the art routing algorithms. This simulator emulates bit reverse, complement, transpose, hotspots, and uniform random traffic patterns and measures the average latency of delivered packets. The results of the simulations showed that WeNMOE outperformed most routing algorithms. The only exception was the XY routing algorithm on uniform random and complement traffic. In these traffic patterns, the traffic load is uniformly distributed, limiting the opportunity for an improved route selection by WeNMOE

A Bio-Inspired Two-Layer Mixed-Signal Flexible Programmable Chip for Early Vision

A bio-inspired model for an analog programmable array processor (APAP), based on studies on the vertebrate retina, has permitted the realization of complex programmable spatio-temporal dynamics in VLSI. This model mimics the way in which images are processed in the visual pathway, what renders a feasible alternative for the implementation of early vision tasks in standard technologies. A prototype chip has been designed and fabricated in 0.5 μm CMOS. It renders a computing power per silicon area and power consumption that is amongst the highest reported for a single chip. The details of the bio-inspired network model, the analog building block design challenges and trade-offs and some functional tests results are presented in this paper.Office of Naval Research (USA) N-000140210884European Commission IST-1999-19007Ministerio de Ciencia y Tecnología TIC1999-082