In recent years, unmanned aerial vehicles (UAVs) have become a key role in wireless communication networks due to their flexibility and dynamic adaptability. However, the openness of UAV-based communications leads to security and privacy concerns in wireless transmissions. This paper investigates a framework of UAV covert communications which introduces flexible reconfigurable intelligent surfaces (F-RIS) in UAV networks. Unlike traditional RIS, F-RIS provides advanced deployment flexibility by conforming to curved surfaces and dynamically reconfiguring its electromagnetic properties to enhance the covert communication performance. We establish an electromagnetic model for F-RIS and further develop a fitted model that describes the relationship between F-RIS reflection amplitude, reflection phase, and incident angle. To maximize the covert transmission rate among UAVs while meeting the covert constraint and public transmission constraint, we introduce a strategy of jointly optimizing UAV trajectories, F-RIS reflection vectors, F-RIS incident angles, and non-orthogonal multiple access (NOMA) power allocation. Considering this is a complicated non-convex optimization problem, we propose a deep reinforcement learning (DRL) algorithm-based optimization solution. Simulation results demonstrate that our proposed framework and optimization method significantly outperform traditional benchmarks, and highlight the advantages of F-RIS in enhancing covert communication performance within UAV networks.

Recent advances in reconfigurable antennas have led to the new concept of the fluid antenna system (FAS) for shape and position flexibility, as another degree of freedom for wireless communication enhancement. This paper explores the integration of a transmit FAS array for hybrid beamforming (HBF) into a reconfigurable intelligent surface (RIS)-assisted communication architecture for multiuser communications in the downlink, corresponding to the downlink RIS-assisted multiuser multiple-input single-output (MISO) FAS model (Tx RIS-assisted-MISO-FAS). By considering Rician channel fading, we formulate a sum-rate maximization optimization problem to alternately optimize the HBF matrix, the RIS phase-shift matrix, and the FAS position. Due to the strong coupling of multiple optimization variables, the multi-fractional summation in the sum-rate expression, the modulus-1 limitation of analog phase shifters and RIS, and the antenna position variables appearing in the exponent, this problem is highly non-convex, which is addressed through the block coordinate descent (BCD) framework in conjunction with semidefinite relaxation (SDR) and majorization-minimization (MM) methods. To reduce the computational complexity, we then propose a low-complexity grating-lobe (GL)-based telescopic-FA (TFA) system with multiple delicately deployed RISs under the sub-connected HBF architecture and the line-of-sight (LoS)-dominant channel condition, to allow closed-form solutions for the HBF and TFA position. Our simulation results illustrate that the former optimization scheme significantly enhances the achievable rate of the proposed system, while the GL-based TFA scheme also provides a considerable gain over conventional fixed-position antenna (FPA) systems, requiring statistical channel state information (CSI) only and with low computational complexity.

Affine frequency division multiplexing (AFDM) is a promising chirp-assisted multicarrier waveform for future high-mobility communications. This paper is devoted to enhanced receiver design for multiple-input–multiple-output AFDM (MIMO-AFDM) systems. Firstly, we introduce a unified variational inference (VI) approach to approximate the target posterior distribution, under which the belief propagation (BP) and expectation propagation (EP)-based algorithms are derived. As both VI-based detection and low-density parity-check (LDPC) decoding can be expressed by bipartite graphs in MIMO-AFDM systems, we construct a joint sparse graph (JSG) by merging the graphs of these two for low-complexity receiver design. Then, based on this graph model, we present the detailed message propagation of the proposed JSG. Additionally, we propose an enhanced JSG (E-JSG) receiver based on the linear constellation encoding model. The proposed E-JSG eliminates the need for interleavers, de-interleavers, and log-likelihood ratio transformations, thus leading to concurrent detection and decoding over the integrated sparse graph. To further reduce detection complexity, we introduce a sparse channel method by approaximating multiple graph edges with insignificant channel coefficients into a single edge on the VI graph. Simulation results show the superiority of the proposed receivers in terms of computational complexity, detection and decoding latency, and error rate performance compared to the conventional ones.

In this paper, we propose a novel active reconfigurable intelligent surface (RIS)-assisted amplitude-domain reflection modulation (ADRM) transmission scheme, termed as ARIS-ADRM. This innovative approach leverages the additional degree of freedom (DoF) provided by the amplitude domain of the active RIS to perform index modulation (IM), thereby enhancing spectral efficiency (SE) without increasing the costs associated with additional radio frequency (RF) chains. Specifically, the ARIS-ADRM scheme transmits information bits through both the modulation symbol and the index of active RIS amplitude allocation patterns (AAPs). To evaluate the performance of the proposed ARIS-ADRM scheme, we provide an achievable rate analysis and derive a closed-form expression for the upper bound on the average bit error probability (ABEP). Furthermore, we formulate an optimization problem to construct the AAP codebook, aiming to minimize the ABEP. Simulation results demonstrate that the proposed scheme significantly improves error performance under the same SE conditions compared to its benchmarks. This improvement is due to its ability to flexibly adapt the transmission rate by fully exploiting the amplitude domain DoF provided by the active RIS.

The integration of aerial reconfigurable intelligent surfaces (ARISs) into IoT networks offers transformative potential for enhancing secure and energy-efficient communication in the presence of blockages and eavesdropping threats. This paper proposes to integrate ARIS into Internet of Things (IoT) networks to simultaneously improve communication reliability, enforce information freshness, and defend against eavesdropping. We formulate a joint optimization problem to minimize the average total transmit energy of IoT devices through the coordinated design of unmanned aerial vehicle (UAV) trajectory, transmit power allocation, ARIS phase shifts, and device scheduling, subject to rigorous constraints on age of information (AoI), UAV energy budget, and secrecy rate guarantees. The optimization problem is formulated as a dynamic programming problem. To address the complexity of long-term dynamic optimization, we employ Lyapunov optimization to decompose it into a per-slot deterministic optimization problem, which can be solved without requiring future state information. However, the per-slot problem is a mixed-integer non-convex optimization problem, making it inherently challenging to solve optimally. To address this, we propose an efficient algorithm that effectively balances the tradeoff between minimizing average total energy consumption and stabilizing average total queue backlogs. Simulation results demonstrate that our algorithm reduces average transmit energy by 46% compared to the round-robin comparison scheme while strictly adhering to information freshness and UAV energy constraints.

As satellite communications play an increasingly important role in future wireless networks, the issue of limited link budget in satellite systems has attracted significant attention in current research. Although semantic communications emerge as a promising solution to address these constraints, it introduces the challenge of increased computational resource consumption in wireless communications. To address these challenges, we propose a multi-layer hybrid bit and generative semantic communication framework which can adapt to the dynamic satellite communication networks. Furthermore, to balance the semantic communication efficiency and performance in satellite-to-ground transmissions, we introduce a novel semantic communication efficiency metric (SEM) that evaluates the trade-offs among latency, computational consumption, and semantic reconstruction quality in the proposed framework. Moreover, we utilize a novel deep reinforcement learning (DRL) algorithm group relative policy optimization (GRPO) to optimize the resource allocation in the proposed network. Simulation results demonstrate the flexibility of our proposed transmission framework and the effectiveness of the proposed metric SEM, illustrate the relationships among various semantic communication metrics.

This paper proposes a novel shape index modulation (SIM) scheme for fluid antenna (FA) systems, termed as FA-SIM, exploiting the dynamic reconfigurability of FA shapes to introduce an additional index dimension for information encoding. By integrating SIM into FA systems, the proposed FA-SIM scheme enhances transmission efficiency and spectral utilization without increasing hardware complexity, offering improved flexibility and performance in next-generation wireless communications. Furthermore, we derive a closed-form expression for the upper bound on the average bit error probability (ABEP), providing theoretical insights into the system's error performance. Simulation results demonstrate that the proposed FA-SIM scheme achieves higher spectral efficiency (SE) than conventional fixed-position antenna systems while maintaining a cost-effective hardware implementation.

Sparse code multiple access (SCMA) is a promising non-orthogonal multiple access scheme for enabling massive connectivity in next generation wireless networks. However, current SCMA codebooks are designed with the same size, leading to inflexibility of user grouping and supporting diverse data rates. To address this issue, we propose a variable modulation SCMA (VM-SCMA) that allows users to employ codebooks with different modulation orders. To guide the VM-SCMA design, a VM matrix (VMM) that assigns modulation orders based on the SCMA factor graph is first introduced. We formulate the VM-SCMA design using the proposed average inverse product distance and the asymptotic upper bound of sum-rate, and jointly optimize the VMM, VM codebooks, power and codebook allocations. The proposed VM-SCMA not only enables diverse date rates but also supports different modulation order combinations for each rate. Leveraging these distinct advantages, we further propose an adaptive VM-SCMA (AVM-SCMA) scheme which adaptively selects the rate and the corresponding VM codebooks to adapt to the users’ channel conditions by maximizing the proposed effective throughput. Simulation results show that the overall designs are able to simultaneously achieve a high-level system flexibility, enhanced error rate results, and significantly improved throughput performance, when compared to conventional SCMA schemes.

In this paper, we propose a novel composition aided generalized quadrature spatial modulation (C-GQSM) scheme to improve the spectral efficiency (SE) of the GQSM systems by exploiting the power domain degree of freedom. The C-GQSM scheme constitutes a hybridization of GQSM and composition modulation (CM) principles, allowing the information bits to encompass not only the antenna activation patterns (AAPs) and amplitude/phase modulated (APM) constellation symbols, but also the energy allocation patterns (EAPs). In addition, we present two low-complexity detection techniques for the proposed C-GQSM system. The first one is based on the ordered successive interference cancellation (OSIC) technique, while the other based on the weighted coordinate descent (WCD) algorithm. Moreover, the upper bound of the average bit error probability (ABEP) of the proposed C-GQSM scheme is derived under both uncorrelated and correlated channel conditions. Simulation results show that the proposed C-GQSM outperforms both the conventional CM and GQSM systems in terms of SE without sacrificing the bit error rate (BER) performance.

In this paper, we propose a fluid antenna (FA) enabled joint transmit and receive index modulation (FA-JTR-IM) transmission mechanism for reconfigurable intelligent surface (RIS)-assisted millimeter-wave (mmWave) communication systems. By integrating the methodologies of FA and IM, the proposed scheme achieves enhanced spectral efficiency (SE) while requiring only a single radio frequency (RF) chain at both the transmitter and receiver. The proposed scheme offers a low hardware cost and power consumption transmission mechanism for the RIS-aided mmWave communication systems. Specifically, the encoding of information bits encompasses not only the modulated symbol but also the indices of transmit FA positions and receive antennas. To achieve a reliability-complexity trade-off, two types of detectors are introduced for the proposed FA-JTR-IM scheme, including the optimal maximum likelihood (ML) detector and two-step sequential (TSS) detector. Based on the ML detector, we derive the expression for the conditional pair-wise error probability of the proposed FA-JTR-IM scheme. Additionally, we provide the closed-form expressions for the unconditional PEP under the finite-path and infinite-path channel conditions, respectively. Simulation results demonstrate the superiority of the proposed FA-JTR-IM scheme in terms of error performance over its conventional benchmark schemes under the same SE condition.

Sparse code multiple access (SCMA) and multiple input multiple output (MIMO) are considered as two efficient techniques to provide both massive connectivity and high spectrum efficiency for future machine-type wireless networks. This paper proposes a single sparse graph (SSG) enhanced expectation propagation algorithm (EPA) receiver, referred to as SSG-EPA, for uplink MIMO-SCMA systems. Firstly, we reformulate the sparse codebook mapping process using a linear encoding model, which transforms the variable nodes (VNs) of SCMA from symbol-level to bit-level VNs. Such transformation facilitates the integration of the VNs of SCMA and low-density parity-check (LDPC), thereby emerging the SCMA and LDPC graphs into a SSG. Subsequently, to further reduce the detection complexity, the message propagation between SCMA VNs and function nodes (FNs) are designed based on EPA principles. Different from the existing iterative detection and decoding (IDD) structure, the proposed EPA-SSG allows a simultaneously detection and decoding at each iteration, and eliminates the use of interleavers, de-interleavers, symbol-to-bit, and bit-to-symbol LLR transformations. Simulation results show that the proposed SSG-EPA achieves better error rate performance compared to the state-of-the-art schemes.

This paper investigates the amalgamation of affine frequency division multiplexing (AFDM) with sparse code multiple access (SCMA), termed as AFDM-SCMA, to facilitate massive connectivity in high-mobility scenarios. We start by introducing the basic principles of SCMA and AFDM systems and then present the proposed AFDM-SCMA system with multiple input and multiple output (MIMO) for both downlink and uplink channels. A two stage detector is proposed for the multi-user detection of the downlink channels. Additionally, to reduce the detection complexity and exploit the channel sparsity, we propose an expectation propagation algorithm (EPA)-aided low complexity receiver for uplink channels. Through numerical simulations, we validate the enhanced performance of the proposed AFDM-SCMA systems compared to conventional orthogonal frequency division multiplexing-empowered SCMA (OFDM-SCMA) systems in terms of error rate performance.

In this paper, we propose a transmission mechanism for fluid antennas (FAs) enabled multiple-input multiple-output (MIMO) communication systems based on index modulation (IM), named FA-IM, which incorporates the principle of IM into FAs-assisted MIMO system to improve the spectral efficiency (SE) without increasing the hardware complexity. In FA-IM, the information bits are mapped not only to the modulation symbols, but also the index of FA position patterns. Additionally, the FA position pattern codebook is carefully designed to further enhance the system performance by maximizing the effective channel gains. Then, a low-complexity detector, referred to efficient sparse Bayesian detector, is proposed by exploiting the inherent sparsity of the transmitted FA-IM signal vectors. Finally, a closed-form expression for the upper bound on the average bit error probability (ABEP) is derived under the finite-path and infinite-path channel condition. Simulation results show that the proposed scheme is capable of improving the SE performance compared to the existing FAs-assisted MIMO and the fixed position antennas (FPAs)-assisted MIMO systems while obviating any additional hardware costs. It has also been shown that the proposed scheme outperforms the conventional FA-assisted MIMO scheme in terms of error performance under the same transmission rate.

In this paper, a novel index and composition modulation (ICM) transmission scheme, termed as grouped generalized composition and spatial modulation (G-GCSM), is proposed for massive multiple-input multiple-output (MIMO) systems. Specifically, it amalgamates the concepts of composition modulation (CM), generalized spatial modulation (GSM) and spatial multiplexing to attain high spectral efficiency (SE) and low implementation complexity. In the G-GCSM scheme, transmit antennas are divided into several groups and the GCSM transmission structure is employed independently in each group, facilitating the bit-to-index mapping issue in massive MIMO scenarios. Additionally, at the receiver side, an improved expectation propagation (EP) detector is designed for the proposed G-GCSM scheme, which exploits the inner sparsity of the transmitted vector in G-GCSM. Simulation results demonstrate the superiority of the proposed scheme over the existing GSM schemes in terms of bit error rate (BER) performance under the same SE conditions. Moreover, the proposed improved EP detector is able to provide a significant performance gain over the conventional minimum-mean-squared error (MMSE) detector in both determined and under-determined massive MIMO systems.

In high-throughput studies of diseases, terms enriched with disease-related genes based on Gene Ontology (GO) are routinely found. However, most current algorithms used to find significant GO terms cannot handle the redundancy that results from the dependencies of GO terms. Simply based on some numerical considerations, current algorithms developed for reducing this redundancy may produce results that do not account for biologically interesting cases. In this article, we present several rules used to design a tool called GO-function for extracting biologically relevant terms from statistically significant GO terms for a disease. Using one gene expression profile for colorectal cancer, we compared GO-function with four algorithms designed to treat redundancy. Then, we validated results obtained in this data set by GO-function using another data set for colorectal cancer. Our analysis showed that GO-function can identify disease-related terms that are more statistically and biologically meaningful than those found by the other four algorithms.

MOTIVATION: Studying the evolutionary conservation of cancer genes can improve our understanding of the genetic basis of human cancers. Functionally related proteins encoded by genes tend to interact with each other in a modular fashion, which may affect both the mode and tempo of their evolution. RESULTS: In the human PPI network, we searched for subnetworks within each of which all proteins have evolved at similar rates since the human and mouse split. Identified at a given co-evolving level, the subnetworks with non-randomly large sizes were defined as co-evolving modules. We showed that proteins within modules tend to be conserved, evolutionarily old and enriched with housekeeping genes, while proteins outside modules tend to be less-conserved, evolutionarily younger and enriched with genes expressed in specific tissues. Viewing cancer genes from co-evolving modules showed that the overall conservation of cancer genes should be mainly attributed to the cancer proteins enriched in the conserved modules. Functional analysis further suggested that cancer proteins within and outside modules might play different roles in carcinogenesis, providing a new hint for studying the mechanism of cancer.

BACKGROUND: Hundreds of genes that are causally implicated in oncogenesis have been found and collected in various databases. For efficient application of these abundant but diverse data sources, it is of fundamental importance to evaluate their consistency. RESULTS: First, we showed that the lists of cancer genes from some major data sources were highly inconsistent in terms of overlapping genes. In particular, most cancer genes accumulated in previous small-scale studies could not be rediscovered in current high-throughput genome screening studies. Then, based on a metric proposed in this study, we showed that most cancer gene lists from different data sources were highly functionally consistent. Finally, we extracted functionally consistent cancer genes from various data sources and collected them in our database F-Census. CONCLUSIONS: Although they have very low gene overlapping, most cancer gene data sources are highly consistent at the functional level, which indicates that they can separately capture partial genes in a few key pathways associated with cancer. Our results suggest that the sample sizes currently used for cancer studies might be inadequate for consistently capturing individual cancer genes, but could be sufficient for finding a number of cancer genes that could represent functionally most cancer genes. The F-Census database provides biologists with a useful tool for browsing and extracting functionally consistent cancer genes from various data sources.

BACKGROUND: Semantic similarity scores for protein pairs are widely applied in functional genomic researches for finding functional clusters of proteins, predicting protein functions and protein-protein interactions, and for identifying putative disease genes. However, because some proteins, such as those related to diseases, tend to be studied more intensively, annotations are likely to be biased, which may affect applications based on semantic similarity measures. Thus, it is necessary to evaluate the effects of the bias on semantic similarity scores between proteins and then find a method to avoid them. RESULTS: First, we evaluated 14 commonly used semantic similarity scores for protein pairs and demonstrated that they significantly correlated with the numbers of annotation terms for the proteins (also known as the protein annotation length). These results suggested that current applications of the semantic similarity scores between proteins might be unreliable. Then, to reduce this annotation bias effect, we proposed normalizing the semantic similarity scores between proteins using the power transformation of the scores. We provide evidence that this improves performance in some applications. CONCLUSIONS: Current semantic similarity measures for protein pairs are highly dependent on protein annotation lengths, which are subject to biological research bias. This affects applications that are based on these semantic similarity scores, especially in clustering studies that rely on score magnitudes. The normalized scores proposed in this paper can reduce the effects of this bias to some extent.

Bioinformatics 23(16), 2121–2128. We would like to correct the author list in this manuscript. We apologize to the two authors Lei Wang and Shaoqi Rao who were missed from the published version of the manuscript. The corrected author list is: Zheng Guo, Lei Wang, Yongjin Li, Xue Gong, Chen Yao, Wencai Ma, Dong Wang, Yanhhui Li, Jing Zhu, Min Zhang, Da Yang, Shaoqi Rao and Jing Wang

MOTIVATION: In microarray studies, numerous tools are available for functional enrichment analysis based on GO categories. Most of these tools, due to their requirement of a prior threshold for designating genes as differentially expressed genes (DEGs), are categorized as threshold-dependent methods that often suffer from a major criticism on their changing results with different thresholds. RESULTS: In the present article, by considering the inherent correlation structure of the GO categories, a continuous measure based on semantic similarity of GO categories is proposed to investigate the functional consistence (or stability) of threshold-dependent methods. The results from several datasets show when simply counting overlapping categories between two groups, the significant category groups selected under different DEG thresholds are seemingly very different. However, based on the semantic similarity measure proposed in this article, the results are rather functionally consistent for a wide range of DEG thresholds. Moreover, we find that the functional consistence of gene lists ranked by SAM metric behaves relatively robust against changing DEG thresholds. AVAILABILITY: Source code in R is available on request from the authors.

MOTIVATION: Differentially expressed gene (DEG) lists detected from different microarray studies for a same disease are often highly inconsistent. Even in technical replicate tests using identical samples, DEG detection still shows very low reproducibility. It is often believed that current small microarray studies will largely introduce false discoveries. RESULTS: Based on a statistical model, we show that even in technical replicate tests using identical samples, it is highly likely that the selected DEG lists will be very inconsistent in the presence of small measurement variations. Therefore, the apparently low reproducibility of DEG detection from current technical replicate tests does not indicate low quality of microarray technology. We also demonstrate that heterogeneous biological variations existing in real cancer data will further reduce the overall reproducibility of DEG detection. Nevertheless, in small subsamples from both simulated and real data, the actual false discovery rate (FDR) for each DEG list tends to be low, suggesting that each separately determined list may comprise mostly true DEGs. Rather than simply counting the overlaps of the discovery lists from different studies for a complex disease, novel metrics are needed for evaluating the reproducibility of discoveries characterized with correlated molecular changes. Supplementaty information: Supplementary data are available at Bioinformatics online.

MOTIVATION: Current high-throughput protein-protein interaction (PPI) data do not provide information about the condition(s) under which the interactions occur. Thus, the identification of condition-responsive PPI sub-networks is of great importance for investigating how a living cell adapts to changing environments. RESULTS: In this article, we propose a novel edge-based scoring and searching approach to extract a PPI sub-network responsive to conditions related to some investigated gene expression profiles. Using this approach, what we constructed is a sub-network connected by the selected edges (interactions), instead of only a set of vertices (proteins) as in previous works. Furthermore, we suggest a systematic approach to evaluate the biological relevance of the identified responsive sub-network by its ability of capturing condition-relevant functional modules. We apply the proposed method to analyze a human prostate cancer dataset and a yeast cell cycle dataset. The results demonstrate that the edge-based method is able to efficiently capture relevant protein interaction behaviors under the investigated conditions. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Microarrays datasets frequently contain a large number of missing values (MVs), which need to be estimated and replaced for subsequent data mining. The focus of the paper is to study the effects of different MV treatments for cDNA microarray data on disease classification analysis. RESULTS: By analyzing five datasets, we demonstrate that among three kinds of classifiers evaluated in this study, support vector machine (SVM) classifiers are robust to varied MV imputation methods [e.g. replacing MVs by zero, K nearest-neighbor (KNN) imputation algorithm, local least square imputation and Bayesian principal component analysis], while the classification and regression tree classifiers are sensitive in terms of classification accuracy. The KNNclassifiers built on differentially expressed genes (DEGs) are robust to the varied MV treatments, but the performances of the KNN classifiers based on all measured genes can be significantly deteriorated when imputing MVs for genes with larger missing rate (MR) (e.g. MR > 5%). Generally, while replacing MVs by zero performs relatively poor, the other imputation algorithms have little difference in affecting classification performances of the SVM or KNN classifiers. We further demonstrate the power and feasibility of our recently proposed functional expression profile (FEP) approach as means to handle microarray data with MVs. The FEPs, which are derived from the functional modules that are enriched with sets of DEGs and thus can be consistently identified under varied MV treatments, achieve precise disease classification with better biological interpretation. We conclude that the choice of MV treatments should be determined in context of the later approaches used for disease classification. The suggested exclusion criterion of ignoring the genes with larger MR (e.g. >5%), while justifiable for some classifiers such as KNN classifiers, might not be considered as a general rule for all classifiers.

BACKGROUND: Development of robust and efficient methods for analyzing and interpreting high dimension gene expression profiles continues to be a focus in computational biology. The accumulated experiment evidence supports the assumption that genes express and perform their functions in modular fashions in cells. Therefore, there is an open space for development of the timely and relevant computational algorithms that use robust functional expression profiles towards precise classification of complex human diseases at the modular level. RESULTS: Inspired by the insight that genes act as a module to carry out a highly integrated cellular function, we thus define a low dimension functional expression profile for data reduction. After annotating each individual gene to functional categories defined in a proper gene function classification system such as Gene Ontology applied in this study, we identify those functional categories enriched with differentially expressed genes. For each functional category or functional module, we compute a summary measure (s) for the raw expression values of the annotated genes to capture the overall activity level of the module. In this way, we can treat the gene expressions within a functional module as an integrative data point to replace the multiple values of individual genes. We compare the classification performance of decision trees based on functional expression profiles with the conventional gene expression profiles using four publicly available datasets, which indicates that precise classification of tumour types and improved interpretation can be achieved with the reduced functional expression profiles. CONCLUSION: This modular approach is demonstrated to be a powerful alternative approach to analyzing high dimension microarray data and is robust to high measurement noise and intrinsic biological variance inherent in microarray data. Furthermore, efficient integration with current biological knowledge has facilitated the interpretation of the underlying molecular mechanisms for complex human diseases at the modular level.