On joint maximum-likelihood estimation of PCR efficiency and initial amount of target

We consider the problem of estimating unknown parameters of the real-time polymerase chain reaction (RTPCR) from noisy observations. The joint ML estimator of the RT-PCR efficiency and the initial number of DNA target molecules is derived. The mean-square error performance of the estimator is studied via simulations. The simulation results indicate that the proposed estimator significantly outperforms a competing technique

ML Estimation of DNA Initial Copy Number in Polymerase Chain Reaction (PCR) Processes

Estimation of DNA copy number in a given biological sample is an extremely important problem in genomics. This problem is especially challenging when the number of the DNA strands is minuscule, which is often the case in applications such as pathogen and genetic mutation detection. A recently developed technique, real-time polymerase chain reaction (PCR), amplifies the number of initial target molecules by replicating them through a series of thermal cycles. Ideally, the number of target molecules doubles at the end of each cycle. However, in practice, due to biochemical noise the efficiency of the PCR reaction, defined as the fraction of target molecules which are successfully copied during a cycle, is always less than 1. In this paper, we formulate the problem of joint maximum-likelihood estimation of the PCR efficiency and the initial DNA copy number. As indicated by simulation studies, the performance of the proposed estimator is superior with respect to competing statistical approaches. Moreover, we compute the Cramer-Rao lower bound on the mean-square estimation error

On Limits of Performance of DNA Microarrays

DNA microarray technology relies on the hybridization process which is stochastic in nature. Probabilistic cross-hybridization of non-specific targets, as well as the shot-noise originating from specific targets binding, are among the many obstacles for achieving high accuracy in DNA microarray analysis. In this paper, we use statistical model of hybridization and cross-hybridization processes to derive a lower bound (viz., the Cramer-Rao bound) on the minimum mean-square error of the target concentrations estimation. A preliminary study of the Cramer-Rao bound for estimating the target concentrations suggests that, in some regimes, cross-hybridization may, in fact, be beneficial—a result with potential ramifications for probe design, which is currently focused on minimizing cross-hybridization

Modeling the kinetics of hybridization in microarrays

Conventional fluorescent-based microarrays acquire data after the hybridization phase. In this phase the targets analytes (i.e., DNA fragments) bind to the capturing probes on the array and supposedly reach a steady state. Accordingly, microarray experiments essentially provide only a single, steady-state data point of the hybridization process. On the other hand, a novel technique (i.e., realtime microarrays) capable of recording the kinetics of hybridization in fluorescent-based microarrays has recently been proposed in [5]. The richness of the information obtained therein promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to the conventional microarrays. In the current paper, we develop a probabilistic model of the kinetics of hybridization and describe a procedure for the estimation of its parameters which include the binding rate and target concentration. This probabilistic model is an important step towards developing optimal detection algorithms for the microarrays which measure the kinetics of hybridization, and to understanding their fundamental limitations

Out-sphere decoder for non-coherent ML SIMO detection and its expected complexity

In multi-antenna communication systems, channel information is often not known at the receiver. To fully exploit the bandwidth resources of the system and ensure the practical feasibility of the receiver, the channel parameters are often estimated and then employed in the design of signal detection algorithms. However, sometimes communication can occur in an environment where learning the channel coefficients becomes infeasible. In this paper we consider the problem of maximum-likelihood (ML)-detection in singleinput multiple-output (SIMO) systems when the channel information is completely unavailable at the receiver and when the employed signalling at the transmitter is q-PSK. It is well known that finding the solution to this optimization requires solving an integer maximization of a quadratic form and is, in general, an NP hard problem. To solve it, we propose an exact algorithm based on the combination of branch and bound tree search and semi-definite program (SDP) relaxation. The algorithm resembles the standard sphere decoder except that, since we are maximizing we need to construct an upper bound at each level of the tree search. We derive an analytical upper bound on the expected complexity of the proposed algorithm

Sphere-constrained ML detection for frequency-selective channels

The maximum-likelihood (ML) sequence detection problem for channels with memory is investigated. The Viterbi algorithm (VA) provides an exact solution. Its computational complexity is linear in the length of the transmitted sequence, but exponential in the channel memory length. On the other hand, the sphere decoding (SD) algorithm also solves the ML detection problem exactly, and has expected complexity which is a low-degree polynomial (often cubic) in the length of the transmitted sequence over a wide range of signal-to-noise ratios. We combine the sphere-constrained search strategy of SD with the dynamic programming principles of the VA. The resulting algorithm has the worst-case complexity determined by the VA, but often significantly lower expected complexity

Iterative decoding for MIMO channels via modified sphere decoding

In recent years, soft iterative decoding techniques have been shown to greatly improve the bit error rate performance of various communication systems. For multiantenna systems employing space-time codes, however, it is not clear what is the best way to obtain the soft information required of the iterative scheme with low complexity. In this paper, we propose a modification of the Fincke-Pohst (sphere decoding) algorithm to estimate the maximum a posteriori probability of the received symbol sequence. The new algorithm solves a nonlinear integer least squares problem and, over a wide range of rates and signal-to-noise ratios, has polynomial-time complexity. Performance of the algorithm, combined with convolutional, turbo, and low-density parity check codes, is demonstrated on several multiantenna channels. The results for systems that employ space-time modulation schemes seem to indicate that the best performing schemes are those that support the highest mutual information between the transmitted and received signals, rather than the best diversity gain

On estimation in real-time microarrays

Conventional fluorescent-based microarrays acquire data after the hybridization phase. During this phase, the target analytes bind to the capturing probes on the array and, by the end of it, supposedly reach a steady state. Therefore, conventional microarrays attempt to detect and quantify the targets with a single data point taken in the steady-state. On the other hand, a novel technique, the so-called real-time microarray, capable of recording the kinetics of hybridization in fluorescent-based microarrays has recently been proposed in (Hassibi, 2007). The richness of the information obtained therein promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to conventional microarrays. In the current paper, we develop a probabilistic model for real-time microarrays and describe a procedure for the estimation of target amounts therein. Moreover, leveraging on system identification ideas, we propose a novel technique for the elimination of cross-hybridization

Signal Processing Aspects of Real-Time DNA Microarrays

Data acquisition in conventional fluorescent-based microarrays takes place after the completion of a hybridization phase. During the hybridization phase, target analytes bind to their corresponding capturing probes on the array. The conventional microarrays attempt to detect presence and quantify amounts of the targets by collecting a single data point, supposedly taken after the hybridization process has reached its steady-state. Recently, so-called real-time microarrays capable of acquiring not only the steady-state data but the entire kinetics of hybridization have been proposed in [1]. The richness of the information obtained by the real-time microarrays promises higher signal-to-noise ratio, smaller estimation error, and broader assay detection dynamic range compared to the conventional microarrays. In the current paper, we study the signal processing aspects of the real-time microarray data acquisition

Blind channel identification based on second-order statistics: a frequency-domain approach

In this communication, necessary and sufficient conditions are presented for the unique blind identification of possibly nonminimum phase channels driven by cyclostationary processes. Using a frequency domain formulation, it is first shown that a channel can be identified by the second-order statistics of the observation if and only if the channel transfer function does not have special uniformly spaced zeros. This condition leads to several necessary and sufficient conditions on the observation spectra and the channel impulse response. Based on the frequency-domain formulation, a new identification algorithm is proposed