Discrete pdf estimation in the presence of noise

The problem of estimating a pdf from measurements has been widely studied by many researchers. However, most of the work was focused on estimating a probability density function of continuous random variables, especially in the absence of noise. In this paper, we consider a model for representing discrete probability density functions based on multirate dsp models. Using this model, we propose an efficient and stable scheme for pdf estimation when the measurements are corrupted by independent additive noise. This approach makes use of well-known results from multirate dsp theory, especially that of biorthogonal partners. Simulation results are given, which clearly show the advantage of the proposed method

Computational identification and analysis of noncoding RNAs - Unearthing the buried treasures in the genome

The central dogma of molecular biology states that the genetic information flows from DNA to RNA to protein. This dogma has exerted a substantial influence on our understanding of the genetic activities in the cells. Under this influence, the prevailing assumption until the recent past was that genes are basically repositories for protein coding information, and proteins are responsible for most of the important biological functions in all cells. In the meanwhile, the importance of RNAs has remained rather obscure, and RNA was mainly viewed as a passive intermediary that bridges the gap between DNA and protein. Except for classic examples such as tRNAs (transfer RNAs) and rRNAs (ribosomal RNAs), functional noncoding RNAs were considered to be rare. However, this view has experienced a dramatic change during the last decade, as systematic screening of various genomes identified myriads of noncoding RNAs (ncRNAs), which are RNA molecules that function without being translated into proteins [11], [40]. It has been realized that many ncRNAs play important roles in various biological processes. As RNAs can interact with other RNAs and DNAs in a sequence-specific manner, they are especially useful in tasks that require highly specific nucleotide recognition [11]. Good examples are the miRNAs (microRNAs) that regulate gene expression by targeting mRNAs (messenger RNAs) [4], [20], and the siRNAs (small interfering RNAs) that take part in the RNAi (RNA interference) pathways for gene silencing [29], [30]. Recent developments show that ncRNAs are extensively involved in many gene regulatory mechanisms [14], [17]. The roles of ncRNAs known to this day are truly diverse. These include transcription and translation control, chromosome replication, RNA processing and modification, and protein degradation and translocation [40], just to name a few. These days, it is even claimed that ncRNAs dominate the genomic output of the higher organisms such as mammals, and it is being suggested that the greater portion of their genome (which does not encode proteins) is dedicated to the control and regulation of cell development [27]. As more and more evidence piles up, greater attention is paid to ncRNAs, which have been neglected for a long time. Researchers began to realize that the vast majority of the genome that was regarded as “junk,” mainly because it was not well understood, may indeed hold the key for the best kept secrets in life, such as the mechanism of alternative splicing, the control of epigenetic variations and so forth [27]. The complete range and extent of the role of ncRNAs are not so obvious at this point, but it is certain that a comprehensive understanding of cellular processes is not possible without understanding the functions of ncRNAs [47]

Identification of CpG islands using a bank of IIR lowpass filters

It has been known that biological sequences such as the DNA sequence display different kinds of patterns depending on their biological functions. This statistical difference can be exploited for identifying the region of interest, such as the protein coding regions or CpG islands, in a new biological sequence that has not been annotated yet. A region of particular interest is the CpG island, which is a region in a DNA sequence that is rich in the dinucleotide CpG, since it is known that they can be used as gene markers. There have been several computational methods for identifying CpG islands, each with its own strength and weakness. In this paper, we propose a novel scheme for detecting CpG islands in a genomic sequence, which is based on a bank of IIR lowpass filters. The proposed method is capable of identifying CpG islands efficiently at a low computational expense. Simulation results are included where appropriate to demonstrate the idea

Optimal alignment algorithm for context-sensitive hidden Markov models

The hidden Markov model is well-known for its efficiency in modeling short-term dependencies between adjacent samples. However, it cannot be used for modeling longer-range interactions between symbols that are distant from each other. In this paper, we introduce the concept of context-sensitive HMM that is capable of modeling strong pairwise correlations between distant symbols. Based on this model, we propose a polynomial-time algorithm that can be used for finding the optimal state sequence of an observed symbol string. The proposed model is especially useful in modeling palindromes, which has an important application in RNA secondary structure analysis

An overview of the role of context-sensitive HMMs in the prediction of ncRNA genes

Non-coding RNAs (ncRNA) are RNA molecules that function in the cells without being translated into proteins. In recent years, much evidence has been found that ncRNAs play a crucial role in various biological processes. As a result, there has been an increasing interest in the prediction of ncRNA genes. Due to the conserved secondary structure in ncRNAs, there exist pairwise dependencies between distant bases. These dependencies cannot be effectively modeled using traditional HMMs, and we need a more complex model such as the context-sensitive HMM (csHMM). In this paper, we overview the role of csHMMs in the RNA secondary structure analysis and the prediction of ncRNA genes. It is demonstrated that the context-sensitive HMMs can serve as an efficient framework for these purposes

Wavelet-based denoising by customized thresholding

The problem of estimating a signal that is corrupted by additive noise has been of interest to many researchers for practical as well as theoretical reasons. Many of the traditional denoising methods have been using linear methods such as the Wiener filtering. Recently, nonlinear methods, especially those based on wavelets have become increasingly popular, due to a number of advantages over the linear methods. It has been shown that wavelet-thresholding has near-optimal properties in the minimax sense, and guarantees better rate of convergence, despite its simplicity. Even though much work has been done in the field of wavelet-thresholding, most of it was focused on statistical modeling of the wavelet coefficients and the optimal choice of the thresholds. In this paper, we propose a custom thresholding function which can improve the denoised results significantly. Simulation results are given to demonstrate the advantage of the new thresholding function

Profile Context-Sensitive HMMs for Probabilistic Modeling of Sequences With Complex Correlations

The profile hidden Markov model is a specific type of HMM that is well suited for describing the common features of a set of related sequences. It has been extensively used in computational biology, where it is still one of the most popular tools. In this paper, we propose a new model called the profile context-sensitive HMM. Unlike traditional profile-HMMs, the proposed model is capable of describing complex long-range correlations between distant symbols in a consensus sequence. We also introduce a general algorithm that can be used for finding the optimal state-sequence of an observed symbol sequence based on the given profile-csHMM. The proposed model has an important application in RNA sequence analysis, especially in modeling and analyzing RNA pseudoknots

Structural Alignment of RNAs Using Profile-csHMMs and Its Application to RNA Homology Search: Overview and New Results

Systematic research on noncoding RNAs (ncRNAs) has revealed that many ncRNAs are actively involved in various biological networks. Therefore, in order to fully understand the mechanisms of these networks, it is crucial to understand the roles of ncRNAs. Unfortunately, the annotation of ncRNA genes that give rise to functional RNA molecules has begun only recently, and it is far from being complete. Considering the huge amount of genome sequence data, we need efficient computational methods for finding ncRNA genes. One effective way of finding ncRNA genes is to look for regions that are similar to known ncRNA genes. As many ncRNAs have well-conserved secondary structures, we need statistical models that can represent such structures for this purpose. In this paper, we propose a new method for representing RNA sequence profiles and finding structural alignment of RNAs based on profile context-sensitive hidden Markov models (profile-csHMMs). Unlike existing models, the proposed approach can handle any kind of RNA secondary structures, including pseudoknots. We show that profile-csHMMs can provide an effective framework for the computational analysis of RNAs and the identification of ncRNA genes

Common factors of the exchange risk premium in emerging European markets

Existing empirical evidence suggests that the Uncovered Interest Rate Parity (UIRP) condition may not hold due to an exchange risk premium. For a panel data set of eleven emerging European economies we decompose this exchange risk premium into an idiosyncratic (country-specific) element and a common factor using a principal components approach. We present evidence of stationary idiosyncratic and common factors. This result leads to the conclusion of a stationary risk premium for these countries, which is consistent with previous studies often documenting a stationary premium in developed countries. Furthermore, we report that the variation in the premium is largely attributable to a common factor influenced by economic developments in the United States.Uncovered Interest Rate Parity, Emerging Economies, Exchange Risk Premiums, Common Factors