Xingpeng Jiang

Functional biogeography of ocean microbes revealed through non-negative matrix factorization.

The direct “metagenomic” sequencing of genomic material from complex assemblages of bacteria, archaea, viruses and microeukaryotes has yielded new insights into the structure of microbial communities. For example, analysis of metagenomic data has revealed the existence of previously unknown microbial taxa whose spatial distributions are limited by environmental conditions, ecological competition, and dispersal mechanisms. However, differences in genotypes that might lead biologists to designate two microbes as taxonomically distinct need not necessarily imply differences in ecological function. Hence, there is a growing need for large-scale analysis of the distribution of microbial function across habitats. Here, we present a framework for investigating the biogeography of microbial function by analyzing the distribution of protein families inferred from environmental sequence data across a global collection of sites. We map over 6,000,000 protein sequences from unassembled reads from the Global Ocean Survey dataset to protein families, generating a protein family relative abundance matrix that describes the distribution of each protein family across sites. We then use non-negative matrix factorization (NMF) to approximate these protein family profiles as linear combinations of a small number of ecological components. Each component has a characteristic functional profile and site profile. Our approach identifies common functional signatures within several of the components. We use our method as a filter to estimate functional distance between sites, and find that an NMF-filtered measure of functional distance is more strongly correlated with environmental distance than a comparable PCA-filtered measure. We also find that functional distance is more strongly correlated with environmental distance than with geographic distance, in agreement with prior studies. We identify similar protein functions in several components and suggest that functional co-occurrence across metagenomic samples could lead to future methods for de-novo functional prediction. We conclude by discussing how NMF, and other dimension reduction methods, can help enable a macroscopic functional description of marine ecosystems.

Neighbor affinity based algorithm for discovering temporal protein complex from dynamic PPI network

Detection of temporal protein complexes would be a great aid in furthering our knowledge of the dynamic features and molecular mechanism in cell life activities. Most existing clustering algorithms for discovering protein complexes are based on static protein interaction networks in which the inherent dynamics are often overlooked. We propose a novel algorithm DPC-NADPIN (Discovering Protein Complexes based on Neighbor Affinity and Dynamic Protein Interaction Network) to identify temporal protein complexes from the time course protein interaction networks. Inspired by the idea of that the tighter a proteins neighbors inside a module connect, the greater the possibility that the protein belongs to the module, DPC-NADPIN algorithm first chooses each of the proteins with high clustering coefficient and its neighbors to consolidate into an initial cluster, and then the initial cluster becomes a protein complex by appending its neighbor proteins according to the relationship between the affinity among neighbors inside the cluster and that outside the cluster. In our experiments, DPC-NADPIN algorithm is proved to be reasonable and it has better performance on discovering protein complexes than the following state-of-the-art algorithms: Hunter, MCODE, CFinder, SPICI, and ClusterONE; Meanwhile, it obtains many protein complexes with strong biological significance, which provide helpful biological knowledge to the related researchers. Moreover, we find that proteins are assembled coordinately to form protein complexes with characteristics of temporality and spatiality, thereby performing specific biological functions.

Microbiome Data Representation by Joint Nonnegative Matrix Factorization with Laplacian Regularization

Microbiome datasets are often comprised of different representations or views which provide complementary information to understand microbial communities, such as metabolic pathways, taxonomic assignments, and gene families. Data integration methods including approaches based on nonnegative matrix factorization (NMF) combine multi-view data to create a comprehensive view of a given microbiome study by integrating multi-view information. In this paper, we proposed a novel variant of NMF which called Laplacian regularized joint non-negative matrix factorization (LJ-NMF) for integrating functional and phylogenetic profiles from HMP. We compare the performance of this method to other variants of NMF. The experimental results indicate that the proposed method offers an efficient framework for microbiome data analysis.

Joint Analysis of Functional and Phylogenetic Composition for Human Microbiome Data

With the advance of high-throughput sequencing technology, it is possible to investigate many complex biological and ecological systems. The objective of Human Microbiome Project (HMP) is to explore the microbial diversity in our human body and to provide experimental and computational standards for subsequent similar studies. The first-stage HMP generated a lot of data for computational analysis and provided a challenge for integration and interpretation of various microbiome data. In this paper, we introduce a data integration method –Laplacian-regularized Joint Non-negative Matrix Factorization (LJ-NMF) for analyzing functional and phylogenetic profiles from HMP jointly. The experimental results indicate that the proposed method offers an efficient framework for microbiome data analysis.

Inferring microbial interaction networks based on consensus similarity network fusion

With the rapid accumulation of high-throughput metagenomic sequencing data, it is possible to infer microbial species relations in a microbial community systematically. In recent years, some approaches have been proposed for identifying microbial interaction network. These methods often focus on one dataset without considering the advantage of data integration. In this study, we propose to use a similarity network fusion (SNF) method to infer microbial relations. The SNF efficiently integrates the similarities of species derived from different datasets by a cross-network diffusion process. We also introduce consensus k-nearest neighborhood (Ck-NN) method instead of k-NN in the original SNF (we call the approach CSNF). The final network represents the augmented species relationships with aggregated evidence from various datasets, taking advantage of complementarity in the data. We apply the method on genus profiles derived from three microbiome datasets and we find that CSNF can discover the modular structure of microbial interaction network which cannot be identified by analyzing a single dataset.

Visualization of genetic disease-phenotype similarities by multiple maps t-SNE with Laplacian regularization.

BackgroundFrom a phenotypic standpoint, certain types of diseases may prove to be difficult to accurately diagnose, due to specific combinations of confounding symptoms. Referred to as phenotypic overlap, these sets of disease-related symptoms suggest shared pathophysiological mechanisms. Few attempts have been made to visualize the phenotypic relationships between different human diseases from a machine learning perspective. The proposed research, it is anticipated, will visually assist researchers in quickly disambiguating symptoms which can confound the timely and accurate diagnosis of a disease.MethodsOur method is primarily based on multiple maps t-SNE (mm-tSNE), which is a probabilistic method for visualizing data points in multiple low dimensional spaces. We improved mm-tSNE by adding a Laplacian regularization term and subsequently provide an algorithm for optimizing the new objective function. The advantage of Laplacian regularization is that it adopts clustering structures of variables and provides more sparsity to the estimated parameters.ResultsIn order to further assess our modified mm-tSNE algorithm from a comparative standpoint, we reexamined two social network datasets used by the previous authors. Subsequently, we apply our method on phenotype dataset. In all these cases, our proposed method demonstrated better performance than the original version of mm-tSNE, as measured by the neighbourhood preservation ratio.ConclusionsPhenotype grouping reflects the nature of human disease genetics. Thus, phenotype visualization may be complementary to investigate candidate genes for diseases as well as functional relations between genes and proteins. These relationships can be modelled by the modified mm-tSNE method. The modified mm-tSNE can be applied directly in other domain including social and biological datasets.

Mining Temporal Protein Complex Based on the Dynamic PIN Weighted with Connected Affinity and Gene Co-Expression

The identification of temporal protein complexes would make great contribution to our knowledge of the dynamic organization characteristics in protein interaction networks (PINs). Recent studies have focused on integrating gene expression data into static PIN to construct dynamic PIN which reveals the dynamic evolutionary procedure of protein interactions, but they fail in practice for recognizing the active time points of proteins with low or high expression levels. We construct a Time-Evolving PIN (TEPIN) with a novel method called Deviation Degree, which is designed to identify the active time points of proteins based on the deviation degree of their own expression values. Owing to the differences between protein interactions, moreover, we weight TEPIN with connected affinity and gene co-expression to quantify the degree of these interactions. To validate the efficiencies of our methods, ClusterONE, CAMSE and MCL algorithms are applied on the TEPIN, DPIN (a dynamic PIN constructed with state-of-the-art three-sigma method) and SPIN (the original static PIN) to detect temporal protein complexes. Each algorithm on our TEPIN outperforms that on other networks in terms of match degree, sensitivity, specificity, F-measure and function enrichment etc. In conclusion, our Deviation Degree method successfully eliminates the disadvantages which exist in the previous state-of-the-art dynamic PIN construction methods. Moreover, the biological nature of protein interactions can be well described in our weighted network. Weighted TEPIN is a useful approach for detecting temporal protein complexes and revealing the dynamic protein assembly process for cellular organization.

Hessian regularization based symmetric nonnegative matrix factorization for clustering gene expression and microbiome data

Nonnegative matrix factorization (NMF) has received considerable attention due to its interpretation of observed samples as combinations of different components, and has been successfully used as a clustering method. As an extension of NMF, Symmetric NMF (SNMF) inherits the advantages of NMF. Unlike NMF, however, SNMF takes a nonnegative similarity matrix as an input, and two lower rank nonnegative matrices (H, HT) are computed as an output to approximate the original similarity matrix. Laplacian regularization has improved the clustering performance of NMF and SNMF. However, Laplacian regularization (LR), as a classic manifold regularization method, suffers some problems because of its weak extrapolating ability. In this paper, we propose a novel variant of SNMF, called Hessian regularization based symmetric nonnegative matrix factorization (HSNMF), for this purpose. In contrast to Laplacian regularization, Hessian regularization fits the data perfectly and extrapolates nicely to unseen data. We conduct extensive experiments on several datasets including text data, gene expression data and HMP (Human Microbiome Project) data. The results show that the proposed method outperforms other methods, which suggests the potential application of HSNMF in biological data clustering.

Detecting temporal protein complexes based on Neighbor Closeness and time course protein interaction networks

The detection of temporal protein complexes would be a great aid in furthering our knowledge of the dynamic features and molecular mechanism in cell life activities. Inspired by the idea of that the tighter a proteins neighbors inside a module connect, the greater the possibility that the protein belongs to the module, we propose a novel clustering algorithm CNC (Clustering based on Neighbor Closeness) and apply it to the time course protein interaction networks (TCPINs) to detect temporal protein complexes. Our novel algorithm has better performance on identifying protein complexes than five state-of-the-art algorithms-Hunter, MCODE, CFinder, SPICI, and ClusterONE-in terms of matching degree and accuracy metric, meanwhile it obtains many protein complexes with strong biological significance.

Inference of microbial interactions from time series data using vector autoregression model

Microbial interaction, such as species competition and symbiotic relationships, plays important role to enable microorganisms to survive by establishing a homeostasis between microbial neighbors and local environments. Thanks to the recent accumulation of large-scale high-throughput sequencing data of complex microbial communities, there are increasing interests in identifying microbial interactions. Computational methods for microbial interactions inference are currently focused on the similarity among microbial individuals (i.e. cooccurrence and correlation patterns), however, less methods considered the dynamics of a single complex community over time. In this paper, we propose to use a multivariate statistical method - Multivariate Vector Autoregression (MVAR) to infer dynamic microbial interactions from the time series of human gut microbiomes. Specifically, we apply MVAR model on a time series data of human gut microbiomes which were treated with repeated antibiotics. The referred microbial interactions identify novel interactions which may provide a novel complementary to similarity or correlation-based methods.