26 research outputs found
Recognizing Speech in a Novel Accent: The Motor Theory of Speech Perception Reframed
The motor theory of speech perception holds that we perceive the speech of
another in terms of a motor representation of that speech. However, when we
have learned to recognize a foreign accent, it seems plausible that recognition
of a word rarely involves reconstruction of the speech gestures of the speaker
rather than the listener. To better assess the motor theory and this
observation, we proceed in three stages. Part 1 places the motor theory of
speech perception in a larger framework based on our earlier models of the
adaptive formation of mirror neurons for grasping, and for viewing extensions
of that mirror system as part of a larger system for neuro-linguistic
processing, augmented by the present consideration of recognizing speech in a
novel accent. Part 2 then offers a novel computational model of how a listener
comes to understand the speech of someone speaking the listener's native
language with a foreign accent. The core tenet of the model is that the
listener uses hypotheses about the word the speaker is currently uttering to
update probabilities linking the sound produced by the speaker to phonemes in
the native language repertoire of the listener. This, on average, improves the
recognition of later words. This model is neutral regarding the nature of the
representations it uses (motor vs. auditory). It serve as a reference point for
the discussion in Part 3, which proposes a dual-stream neuro-linguistic
architecture to revisits claims for and against the motor theory of speech
perception and the relevance of mirror neurons, and extracts some implications
for the reframing of the motor theory
Fast MCMC sampling for hidden markov models to determine copy number variations
<p>Abstract</p> <p>Background</p> <p>Hidden Markov Models (HMM) are often used for analyzing Comparative Genomic Hybridization (CGH) data to identify chromosomal aberrations or copy number variations by segmenting observation sequences. For efficiency reasons the parameters of a HMM are often estimated with maximum likelihood and a segmentation is obtained with the Viterbi algorithm. This introduces considerable uncertainty in the segmentation, which can be avoided with Bayesian approaches integrating out parameters using Markov Chain Monte Carlo (MCMC) sampling. While the advantages of Bayesian approaches have been clearly demonstrated, the likelihood based approaches are still preferred in practice for their lower running times; datasets coming from high-density arrays and next generation sequencing amplify these problems.</p> <p>Results</p> <p>We propose an approximate sampling technique, inspired by compression of discrete sequences in HMM computations and by <it>kd</it>-trees to leverage spatial relations between data points in typical data sets, to speed up the MCMC sampling.</p> <p>Conclusions</p> <p>We test our approximate sampling method on simulated and biological ArrayCGH datasets and high-density SNP arrays, and demonstrate a speed-up of 10 to 60 respectively 90 while achieving competitive results with the state-of-the art Bayesian approaches.</p> <p><it>Availability: </it>An implementation of our method will be made available as part of the open source GHMM library from <url>http://ghmm.org</url>.</p
Modeling the Evolution of Regulatory Elements by Simultaneous Detection and Alignment with Phylogenetic Pair HMMs
The computational detection of regulatory elements in DNA is a difficult but important problem impacting our progress in understanding the complex nature of eukaryotic gene regulation. Attempts to utilize cross-species conservation for this task have been hampered both by evolutionary changes of functional sites and poor performance of general-purpose alignment programs when applied to non-coding sequence. We describe a new and flexible framework for modeling binding site evolution in multiple related genomes, based on phylogenetic pair hidden Markov models which explicitly model the gain and loss of binding sites along a phylogeny. We demonstrate the value of this framework for both the alignment of regulatory regions and the inference of precise binding-site locations within those regions. As the underlying formalism is a stochastic, generative model, it can also be used to simulate the evolution of regulatory elements. Our implementation is scalable in terms of numbers of species and sequence lengths and can produce alignments and binding-site predictions with accuracy rivaling or exceeding current systems that specialize in only alignment or only binding-site prediction. We demonstrate the validity and power of various model components on extensive simulations of realistic sequence data and apply a specific model to study Drosophila enhancers in as many as ten related genomes and in the presence of gain and loss of binding sites. Different models and modeling assumptions can be easily specified, thus providing an invaluable tool for the exploration of biological hypotheses that can drive improvements in our understanding of the mechanisms and evolution of gene regulation
Computational Analysis of Whole-Genome Differential Allelic Expression Data in Human
Allelic imbalance (AI) is a phenomenon where the two alleles of a given gene are expressed at different levels in a given cell, either because of epigenetic inactivation of one of the two alleles, or because of genetic variation in regulatory regions. Recently, Bing et al. have described the use of genotyping arrays to assay AI at a high resolution (∼750,000 SNPs across the autosomes). In this paper, we investigate computational approaches to analyze this data and identify genomic regions with AI in an unbiased and robust statistical manner. We propose two families of approaches: (i) a statistical approach based on z-score computations, and (ii) a family of machine learning approaches based on Hidden Markov Models. Each method is evaluated using previously published experimental data sets as well as with permutation testing. When applied to whole genome data from 53 HapMap samples, our approaches reveal that allelic imbalance is widespread (most expressed genes show evidence of AI in at least one of our 53 samples) and that most AI regions in a given individual are also found in at least a few other individuals. While many AI regions identified in the genome correspond to known protein-coding transcripts, others overlap with recently discovered long non-coding RNAs. We also observe that genomic regions with AI not only include complete transcripts with consistent differential expression levels, but also more complex patterns of allelic expression such as alternative promoters and alternative 3′ end. The approaches developed not only shed light on the incidence and mechanisms of allelic expression, but will also help towards mapping the genetic causes of allelic expression and identify cases where this variation may be linked to diseases
Global Chromatin Domain Organization of the Drosophila Genome
In eukaryotes, neighboring genes can be packaged together in specific chromatin structures that ensure their coordinated expression. Examples of such multi-gene chromatin domains are well-documented, but a global view of the chromatin organization of eukaryotic genomes is lacking. To systematically identify multi-gene chromatin domains, we constructed a compendium of genome-scale binding maps for a broad panel of chromatin-associated proteins in Drosophila melanogaster. Next, we computationally analyzed this compendium for evidence of multi-gene chromatin domains using a novel statistical segmentation algorithm. We find that at least 50% of all fly genes are organized into chromatin domains, which often consist of dozens of genes. The domains are characterized by various known and novel combinations of chromatin proteins. The genes in many of the domains are coregulated during development and tend to have similar biological functions. Furthermore, during evolution fewer chromosomal rearrangements occur inside chromatin domains than outside domains. Our results indicate that a substantial portion of the Drosophila genome is packaged into functionally coherent, multi-gene chromatin domains. This has broad mechanistic implications for gene regulation and genome evolution
Network dimensioning and base station on/off switching strategies for sustainable deployments in remote areas
This paper provides a methodology for the dimensioning of the access network in remote rural areas, considering the progressive introduction of cellular services in these regions. A 3G small cell (SC) network with one or several carriers deployed at the SC, fed with solar panels and connected to a backhaul with limited capacity is considered for the analysis. Because the backhaul may be inexistent or very expensive (e.g., satellite-based backhaul) the network design pursues the minimization of the required backhaul bandwidth. The required backhaul bandwidth and the required energy units (i.e., the size of the solar panels and the required number of batteries) are then obtained as an output of the dimensioning analysis. Both the backhaul minimization objective and the constraints associated with each of the carriers (low maximum radiated power and low number of users connected simultaneously) require a novel methodology compared to the classical dimensioning techniques. We also develop a procedure for switching on/off carriers in order to minimize the energy consumption without affecting the quality of service (QoS) perceived by the users. This technique allows reducing the required size of the energy units, which directly translates into a cost reduction. In the development of this on/off switching strategy, we first assume perfect knowledge of the traffic profile and later, we develop a robust Bayesian approach to account for possible error modeling in the traffic profile information.Peer ReviewedPostprint (published version