Systems biology intertwines with single cell and AI.

A report of the 12th International Conference on Systems Biology (ISB2018), 18-21 August, Guiyang, China.

CEA: Combination-based gene set functional enrichment analysis.

Functional enrichment analysis is a fundamental and challenging task in bioinformatics. Most of the current enrichment analysis approaches individually evaluate functional terms and often output a list of enriched terms with high similarity and redundancy, which makes it difficult for downstream studies to extract the underlying biological interpretation. In this paper, we proposed a novel framework to assess the performance of combination-based enrichment analysis.

Integrating data- and model-driven strategies in systems biology.

A report of the 11th International Conference on Systems Biology (ISB2017), 18-21 August, Shenzhen, China.

Understanding biological systems through the lens of data.

A report of the 10th International Conference on Systems Biology (ISB2016), 19-22 August, Weihai, China.

NetGen: a novel network-based probabilistic generative model for gene set functional enrichment analysis.

Background: High-throughput experimental techniques have been dramatically improved and widely applied in the past decades. However, biological interpretation of the high-throughput experimental results, such as differential expression gene sets derived from microarray or RNA-seq experiments, is still a challenging task. Gene Ontology (GO) is commonly used in the functional enrichment studies.

NCC-AUC: an AUC optimization method to identify multi-biomarker panel for cancer prognosis from genomic and clinical data.

Motivation: In prognosis and survival studies, an important goal is to identify multi-biomarker panels with predictive power using molecular characteristics or clinical observations. Such analysis is often challenged by censored, small-sample-size, but high-dimensional genomic profiles or clinical data. Therefore, sophisticated models and algorithms are in pressing need.

Discovery of co-occurring driver pathways in cancer.

Background: It has been widely realized that pathways rather than individual genes govern the course of carcinogenesis. Therefore, discovering driver pathways is becoming an important step to understand the molecular mechanisms underlying cancer and design efficient treatments for cancer patients. Previous studies have focused mainly on observation of the alterations in cancer genomes at the individual gene or single pathway level.

Corbi: a new R package for biological network alignment and querying.

In the last decade, plenty of biological networks are built from the large scale experimental data produced by the rapidly developing high-throughput techniques as well as literature and other sources. But the huge amount of network data have not been fully utilized due to the limited biological network analysis tools. As a basic and essential bioinformatics method, biological network alignment and querying have been applied in many fields such as predicting new protein-protein interactions (PPI).

Identification of mutated core cancer modules by integrating somatic mutation, copy number variation, and gene expression data.

Motivation: Understanding the molecular mechanisms underlying cancer is an important step for the effective diagnosis and treatment of cancer patients. With the huge volume of data from the large-scale cancer genomics projects, an open challenge is to distinguish driver mutations, pathways, and gene sets (or core modules) that contribute to cancer formation and progression from random passengers which accumulate in somatic cells but do not contribute to tumorigenesis. Due to mutational heterogeneity, current analyses are often restricted to known pathways and functional modules for enrichment of somatic mutations.

Computational systems biology in the big data era.

A report of the 6th IEEE International Conference on Systems Biology (IEEE ISB2012), 18-20 August, Xi'an, China.

Breast tumor subgroups reveal diverse clinical prognostic power.

Predicting the outcome of cancer therapies using molecular features and clinical observations is a key goal of cancer biology, which has been addressed comprehensively using whole patient datasets without considering the effect of tumor heterogeneity. We hypothesized that molecular features and clinical observations have different prognostic abilities for different cancer subtypes, and made a systematic study using both clinical observations and gene expression data. This analysis revealed that (1) gene expression profiles and clinical features show different prognostic power for the five breast cancer subtypes; (2) gene expression data of the normal-like subgroup contains more valuable prognostic information and survival associated contexts than the other subtypes, and the patient survival time of the normal-like subtype is more predictable based on the gene expression profiles; and (3) the prognostic power of many previously reported breast cancer gene signatures increased in the normal-like subtype and reduced in the other subtypes compared with that in the whole sample set.

Cancer stem cells display extremely large evolvability: alternating plastic and rigid networks as a potential Mechanism: network models, novel therapeutic target strategies, and the contributions of hypoxia, inflammation and cellular senescence.

Cancer is increasingly perceived as a systems-level, network phenomenon. The major trend of malignant transformation can be described as a two-phase process, where an initial increase of network plasticity is followed by a decrease of plasticity at late stages of tumor development. The fluctuating intensity of stress factors, like hypoxia, inflammation and the either cooperative or hostile interactions of tumor inter-cellular networks, all increase the adaptation potential of cancer cells.

Discovering link communities in complex networks by an integer programming model and a genetic algorithm.

Identification of communities in complex networks is an important topic and issue in many fields such as sociology, biology, and computer science. Communities are often defined as groups of related nodes or links that correspond to functional subunits in the corresponding complex systems. While most conventional approaches have focused on discovering communities of nodes, some recent studies start partitioning links to find overlapping communities straightforwardly.

Discovery of cell-type specific regulatory elements in the human genome using differential chromatin modification analysis.

Chromatin modifications have been comprehensively illustrated to play important roles in gene regulation and cell diversity in recent years. Given the rapid accumulation of genome-wide chromatin modification maps across multiple cell types, there is an urgent need for computational methods to analyze multiple maps to reveal combinatorial modification patterns and define functional DNA elements, especially those are specific to cell types or tissues. In this current study, we developed a computational method using differential chromatin modification analysis (dCMA) to identify cell-type-specific genomic regions with distinctive chromatin modifications.

iPcc: a novel feature extraction method for accurate disease class discovery and prediction.

Gene expression profiling has gradually become a routine procedure for disease diagnosis and classification. In the past decade, many computational methods have been proposed, resulting in great improvements on various levels, including feature selection and algorithms for classification and clustering. In this study, we present iPcc, a novel method from the feature extraction perspective to further propel gene expression profiling technologies from bench to bedside.

APG: an Active Protein-Gene network model to quantify regulatory signals in complex biological systems.

Synergistic interactions among transcription factors (TFs) and their cofactors collectively determine gene expression in complex biological systems. In this work, we develop a novel graphical model, called Active Protein-Gene (APG) network model, to quantify regulatory signals of transcription in complex biomolecular networks through integrating both TF upstream-regulation and downstream-regulation high-throughput data. Firstly, we theoretically and computationally demonstrate the effectiveness of APG by comparing with the traditional strategy based only on TF downstream-regulation information.

ellipsoidFN: a tool for identifying a heterogeneous set of cancer biomarkers based on gene expressions.

Computationally identifying effective biomarkers for cancers from gene expression profiles is an important and challenging task. The challenge lies in the complicated pathogenesis of cancers that often involve the dysfunction of many genes and regulatory interactions. Thus, sophisticated classification model is in pressing need.

GOMA: functional enrichment analysis tool based on GO modules.

Analyzing the function of gene sets is a critical step in interpreting the results of high-throughput experiments in systems biology. A variety of enrichment analysis tools have been developed in recent years, but most output a long list of significantly enriched terms that are often redundant, making it difficult to extract the most meaningful functions. In this paper, we present GOMA, a novel enrichment analysis method based on the new concept of enriched functional Gene Ontology (GO) modules.

De novo prediction of RNA-protein interactions from sequence information.

Protein-RNA interactions are fundamentally important in understanding cellular processes. In particular, non-coding RNA-protein interactions play an important role to facilitate biological functions in signalling, transcriptional regulation, and even the progression of complex diseases. However, experimental determination of protein-RNA interactions remains time-consuming and labour-intensive.

Revealing metabolite biomarkers for acupuncture treatment by linear programming based feature selection.

Background: Acupuncture has been practiced in China for thousands of years as part of the Traditional Chinese Medicine (TCM) and has gradually accepted in western countries as an alternative or complementary treatment. However, the underlying mechanism of acupuncture, especially whether there exists any difference between varies acupoints, remains largely unknown, which hinders its widespread use.

Results: In this study, we develop a novel Linear Programming based Feature Selection method (LPFS) to understand the mechanism of acupuncture effect, at molecular level, by revealing the metabolite biomarkers for acupuncture treatment.

Inferring domain-domain interactions from protein-protein interactions in the complex network conformation.

Background: As protein domains are functional and structural units of proteins, a large proportion of protein-protein interactions (PPIs) are achieved by domain-domain interactions (DDIs), many computational efforts have been made to identify DDIs from experimental PPIs since high throughput technologies have produced a large number of PPIs for different species. These methods can be separated into two categories: deterministic and probabilistic. In deterministic methods, parsimony assumption has been utilized.

Modelling biological systems from molecules to dynamical networks.

A report of the 5th IEEE International Conference on Systems Biology (IEEE ISB2011), 2-4 September 2011, Zhuhai, China.

Potts model based on a Markov process computation solves the community structure problem effectively.

The Potts model is a powerful tool to uncover community structure in complex networks. Here, we propose a framework to reveal the optimal number of communities and stability of network structure by quantitatively analyzing the dynamics of the Potts model. Specifically we model the community structure detection Potts procedure by a Markov process, which has a clear mathematical explanation.

Common community structure in time-varying networks.

In this report we introduce the concept of common community structure in time-varying networks. We propose a novel optimization algorithm to rapidly detect common community structure in such networks. Both theoretical and numerical results show that the proposed method not only can resolve detailed common communities, but also can effectively identify the dynamical phenomena in time-varying networks.

Efficient methods for identifying mutated driver pathways in cancer.

Motivation: The first step for clinical diagnostics, prognostics and targeted therapeutics of cancer is to comprehensively understand its molecular mechanisms. Large-scale cancer genomics projects are providing a large volume of data about genomic, epigenomic and gene expression aberrations in multiple cancer types. One of the remaining challenges is to identify driver mutations, driver genes and driver pathways promoting cancer proliferation and filter out the unfunctional and passenger ones.