Jianqiu Zhang

Review of Peak Detection Algorithms in Liquid-Chromatography-Mass Spectrometry

In this review, we will discuss peak detection in Liquid-Chromatography-Mass Spectrometry (LC/MS) from a signal processing perspective. A brief introduction to LC/MS is followed by a description of the major processing steps in LC/MS. Specifically, the problem of peak detection is formulated and various peak detection algorithms are described and compared.

Mathematical modeling and stability analysis of macrophage activation in left ventricular remodeling post-myocardial infarction

BackgroundAbout 6 million Americans suffer from heart failure and 70% of heart failure cases are caused by myocardial infarction (MI). Following myocardial infarction, increased cytokines induce two major types of macrophages: classically activated macrophages which contribute to extracellular matrix destruction and alternatively activated macrophages which contribute to extracellular matrix construction. Though experimental results have shown the transitions between these two types of macrophages, little is known about the dynamic progression of macrophages activation. Therefore, the objective of this study is to analyze macrophage activation patterns post-MI.ResultsWe have collected experimental data from adult C57 mice and built a framework to represent the regulatory relationships among cytokines and macrophages. A set of differential equations were established to characterize the regulatory relationships for macrophage activation in the left ventricle post-MI based on the physical chemistry laws. We further validated the mathematical model by comparing our computational results with experimental results reported in the literature. By applying Lyaponuv stability analysis, the established mathematical model demonstrated global stability in homeostasis situation and bounded response to myocardial infarction.ConclusionsWe have established and validated a mathematical model for macrophage activation post-MI. The stability analysis provided a possible strategy to intervene the balance of classically and alternatively activated macrophages in this study. The results will lay a strong foundation to understand the mechanisms of left ventricular remodelling post-MI.

Joint estimation and decoding of space-time Trellis codes

We explore the possibility of using an emerging tool in statistical signal processing, sequential importance sampling (SIS), for joint estimation and decoding of space-time trellis codes (STTC). First, we provide background on SIS, and then we discuss its application to space-time trellis code (STTC) systems. It is shown through simulations that SIS is suitable for joint estimation and decoding of STTC with time-varying flat-fading channels when phase ambiguity is avoided. We used a design criterion for STTCs and temporally correlated channels that combats phase ambiguity without pilot signaling. We have shown by simulations that the design is valid.

Bayesian inference of genetic regulatory networks from time series microarray data using dynamic Bayesian networks

Reverse engineering of genetic regulatory networks from time series microarray data are investigated. We propose a dynamic Bayesian networks (DBNs) modeling and a full Bayesian learning scheme. The proposed DBN directly models the continuous expression levels and also is associated with parameters that indicate the degree as well as the type of regulations. To learn the network from data, we proposed a reversible jump Markov chain Monte Carlo (RJMCMC) algorithm. The RJMCMC algorithm can provide not only more accurate inference results than the deterministic alternative algorithms but also an estimate of the a posteriori probabilities (APPs) of the network topology. The estimated APPs provide useful information on the confidence of the inferred results and can also be used for efficient Bayesian data integration. The proposed approach is tested on yeast cell cycle microarray data and the results are compared with the KEGG pathway map.

Reverse Engineering Yeast Gene Regulatory Networks using Graphical Models

We investigate in this paper reverse engineering of gene regulatory networks from time series microarray data. We propose a dynamic Bayesian networks (DBNs) modeling and a full Bayesian learning scheme. The proposed DBN models directly the continuous expression levels and also is associated with parameters that indicate the degree as well as the types of regulations. To learn the network from data, we proposed a reversible jump Markov chain Monte Carlo (RJMCMC) algorithm. The RJMCMC algorithm can provide not only more accurate inference results than the deterministic alternative algorithms but also an estimate on the a posteriori probabilities (APPs) of the network topology. The estimated APPs provide useful information on the confidence of the inferred results and can also be used for efficient Bayesian data integration. The proposed approach was tested on yeast cell cycle microarray data and the results were compared with the KEGG pathway map

Adaptive blind multiuser detection over flat fast fading channels using particle filtering

In this paper, we propose a method for blind multiuser detection (MUD) in synchronous systems over flat and fast Rayleigh fading channels. We adopt an autoregressive-moving-average (ARMA) process to model the temporal correlation of the channels. Based on the ARMA process, we propose a novel time-observation state space model (TOSSM) that describes the dynamics of the addressed multiuser system. The TOSSM allows an MUD with natural blending of low complexity particle filtering (PF) and mixture Kalman filtering (for channel estimation). We further propose to use a more efficient PF algorithm known as the stochastic M-algorithm (SMA), which, although having lower complexity than the generic PF implementation, maintains comparable performance.

Bayesian Peptide Peak Detection for High Resolution TOF Mass Spectrometry

In this paper, we address the issue of peptide ion peak detection for high resolution time-of-flight (TOF) mass spectrometry (MS) data. A novel Bayesian peptide ion peak detection method is proposed for TOF data with resolution of 10 000-15 000 full width at half-maximum (FWHW). MS spectra exhibit distinct characteristics at this resolution, which are captured in a novel parametric model. Based on the proposed parametric model, a Bayesian peak detection algorithm based on Markov chain Monte Carlo (MCMC) sampling is developed. The proposed algorithm is tested on both simulated and real datasets. The results show a significant improvement in detection performance over a commonly employed method. The results also agree with experts visual inspection. Moreover, better detection consistency is achieved across MS datasets from patients with identical pathological condition.

BPDA - A Bayesian peptide detection algorithm for mass spectrometry

BackgroundMass spectrometry (MS) is an essential analytical tool in proteomics. Many existing algorithms for peptide detection are based on isotope template matching and usually work at different charge states separately, making them ineffective to detect overlapping peptides and low abundance peptides.ResultsWe present BPDA, a Bayesian approach for peptide detection in data produced by MS instruments with high enough resolution to baseline-resolve isotopic peaks, such as MALDI-TOF and LC-MS. We model the spectra as a mixture of candidate peptide signals, and the model is parameterized by MS physical properties. BPDA is based on a rigorous statistical framework and avoids problems, such as voting and ad-hoc thresholding, generally encountered in algorithms based on template matching. It systematically evaluates all possible combinations of possible peptide candidates to interpret a given spectrum, and iteratively finds the best fitting peptide signal in order to minimize the mean squared error of the inferred spectrum to the observed spectrum. In contrast to previous detection methods, BPDA performs deisotoping and deconvolution of mass spectra simultaneously, which enables better identification of weak peptide signals and produces higher sensitivities and more robust results. Unlike template-matching algorithms, BPDA can handle complex data where features overlap. Our experimental results indicate that BPDA performs well on simulated data and real MS data sets, for various resolutions and signal to noise ratios, and compares very favorably with commonly used commercial and open-source software, such as flexAnalysis, OpenMS, and Decon2LS, according to sensitivity and detection accuracy.ConclusionUnlike previous detection methods, which only employ isotopic distributions and work at each single charge state alone, BPDA takes into account the charge state distribution as well, thus lending information to better identify weak peptide signals and produce more robust results. The proposed approach is based on a rigorous statistical framework, which avoids problems generally encountered in algorithms based on template matching. Our experiments indicate that BPDA performs well on both simulated data and real data, and compares very favorably with commonly used commercial and open-source software. The BPDA software can be downloaded from http://gsp.tamu.edu/Publications/supplementary/sun10a/bpda.

PeakLink: a new peptide peak linking method in LC-MS/MS using wavelet and SVM

MOTIVATION In liquid chromatography-mass spectrometry/tandem mass spectrometry (LC-MS/MS), it is necessary to link tandem MS-identified peptide peaks so that protein expression changes between the two runs can be tracked. However, only a small number of peptides can be identified and linked by tandem MS in two runs, and it becomes necessary to link peptide peaks with tandem identification in one run to their corresponding ones in another run without identification. In the past, peptide peaks are linked based on similarities in retention time (rt), mass or peak shape after rt alignment, which corrects mean rt shifts between runs. However, the accuracy in linking is still limited especially for complex samples collected from different conditions. Consequently, large-scale proteomics studies that require comparison of protein expression profiles of hundreds of patients can not be carried out effectively. METHOD In this article, we consider the problem of linking peptides from a pair of LC-MS/MS runs and propose a new method, PeakLink (PL), which uses information in both the time and frequency domain as inputs to a non-linear support vector machine (SVM) classifier. The PL algorithm first uses a threshold on an rt likelihood ratio score to remove candidate corresponding peaks with excessively large elution time shifts, then PL calculates the correlation between a pair of candidate peaks after reducing noise through wavelet transformation. After converting rt and peak shape correlation to statistical scores, an SVM classifier is trained and applied for differentiating corresponding and non-corresponding peptide peaks. RESULTS PL is tested in multiple challenging cases, in which LC-MS/MS samples are collected from different disease states, different instruments and different laboratories. Testing results show significant improvement in linking accuracy compared with other algorithms. AVAILABILITY AND IMPLEMENTATION M files for the PL alignment method are available at http://compgenomics.utsa.edu/zgroup/PeakLink. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Uncover cooperative gene regulations by microRNAs and transcription factors in glioblastoma using a nonnegative hybrid factor model

Transcriptional regulation by transcription factors (TFs) and microRNAs controls when and how much RNA is created. Due to technical limitations, the protein level expressions of TFs are usually unknown, making computational reconstruction of transcriptional network a difficult task. We proposed here a novel Bayesian nonnegative hybrid factor model for transcriptional network modeling, which is capable to estimate both the non-negative abundances of the transcription factors, the regulatory effects of TFs and microRNAs, and the sample clustering information by integrating microarray data and existing knowledge regarding TFs and microRNAs regulated target genes. The results demonstrated its validity and effectiveness to reconstructing transcriptional networks through simulated systems and real data.