Fr243 THE FIRST SYSTEMS BIOLOGY APPROACH TO THE MICROBIOME OF SIBO BY HIGH-LEVEL CO-OCCURRENCE COMMUNITY NETWORK ANALYSES IDENTIFIES TWO DISTINCT PROTEOBACTERIA-RELATED CLUSTERS

Abstract Background: Treg cells function in the immune homeostasis, these cells express high level of CD25. Even though the molecular mechanisms of CD25-mediated signaling pathways has been reported, some questions are still unclear, e.g. the relationship and function of the relative lncRNA. It is known that the CD25 expression levels are various among different cancers. Thus, we intended to dissect systems biology of a lncRNA pertained to CD25 and CD25 protein interactors-targeting miRNAs. Methods: Apart from using the available RNA-seq data, the co-expression analysis of the lncRNA pertained to some cancers was performed. Our analysis was done for protein interactors of CD25 by STRING 11.0, ShinyGO v0.60 and KEGG web servers were used for enrichment and network analysis of CD25. TargetScan 7.2, miRTargetLink Human and mirDIP were applied for determining the CD25 and CD25 interactors-targeting miRNAs. To find the lncRNA-miRNA and lncRNA-protein interactions, starBase v3.0, LncBase Predicted v.2 and SFPEL-LPI were recruited, respectively. Also, using Co-LncRNA, the co-expressed lncRNA analysis and the relative signaling pathways in some cancers including bladder, breast, head and neck, kidney, liver, lung, prostate and thyroid cancers using RNA-seq data were achieved. Results: OIP5-AS1 was shown to have the interaction with CD25 and CD25 protein interactors-targeting miRNAs. In addition, the co-expression of OIP5-AS1 in cancers and their signaling pathways was identified. Conclusions: Possibly, OIP5-AS1 can effect on CD25 expression in all relative signaling pathways of these cancers.

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Hematopoiesis and its disorders: a systems biology approach

Blood ◽

10.1182/blood-2009-08-215798 ◽

2010 ◽

Vol 115 (12) ◽

pp. 2339-2347 ◽

Cited By ~ 36

Author(s):

Zakary L. Whichard ◽

Casim A. Sarkar ◽

Marek Kimmel ◽

Seth J. Corey

Keyword(s):

Systems Biology ◽

High Throughput Screening ◽

Myeloid Leukemia ◽

Building Blocks ◽

Imatinib Resistance ◽

Computing Power ◽

Cell Production ◽

Daughter Cells ◽

Cyclical Neutropenia ◽

High Level

Scientists have traditionally studied complex biologic systems by reducing them to simple building blocks. Genome sequencing, high-throughput screening, and proteomics have, however, generated large datasets, revealing a high level of complexity in components and interactions. Systems biology embraces this complexity with a combination of mathematical, engineering, and computational tools for constructing and validating models of biologic phenomena. The validity of mathematical modeling in hematopoiesis was established early by the pioneering work of Till and McCulloch. In reviewing more recent papers, we highlight deterministic, stochastic, statistical, and network-based models that have been used to better understand a range of topics in hematopoiesis, including blood cell production, the periodicity of cyclical neutropenia, stem cell production in response to cytokine administration, and the emergence of imatinib resistance in chronic myeloid leukemia. Future advances require technologic improvements in computing power, imaging, and proteomics as well as greater collaboration between experimentalists and modelers. Altogether, systems biology will improve our understanding of normal and abnormal hematopoiesis, better define stem cells and their daughter cells, and potentially lead to more effective therapies.

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Cortical 3-hinges could serve as hubs in cortico-cortical connective network

Brain Imaging and Behavior ◽

10.1007/s11682-019-00204-6 ◽

2020 ◽

Vol 14 (6) ◽

pp. 2512-2529

Author(s):

Tuo Zhang ◽

Xiao Li ◽

Xi Jiang ◽

Fangfei Ge ◽

Shu Zhang ◽

...

Keyword(s):

Brain Function ◽

Functional Networks ◽

Functional Brain ◽

Network Analyses ◽

Folding Pattern ◽

New Findings ◽

Cortical Parcellation ◽

High Level ◽

Human Brains ◽

Anatomical Connection

Abstract Mapping the relation between cortical convolution and structural/functional brain architectures could provide deep insights into the mechanisms of brain development, evolution and diseases. In our previous studies, we found a unique gyral folding pattern, termed a 3-hinge, which was defined as the conjunction of three gyral crests. The uniqueness of the 3-hinge was evidenced by its thicker cortex and stronger fiber connections than other gyral regions. However, the role that 3-hinges play in cortico-cortical connective architecture remains unclear. To this end, we conducted MRI studies by constructing structural cortico-cortical connective networks based on a fine-granular cortical parcellation, the parcels of which were automatically labeled as 3-hinge, 2-hinge (ordinary gyrus) or sulcus. On human brains, 3-hinges possess significantly higher degrees, strengths and betweennesses than 2-hinges, suggesting that 3-hinges could serve more like hubs in the cortico-cortical connective network. This hypothesis gains supports from human functional network analyses, in which 3-hinges are involved in more global functional networks than ordinary gyri. In addition, 3-hinges could serve as ‘connector’ hubs rather than ‘provincial’ hubs and they account for a dominant proportion of nodes in the high-level ‘backbone’ of the network. These structural results are reproduced on chimpanzee and macaque brains, while the roles of 3-hinges as hubs become more pronounced in higher order primates. Our new findings could provide a new window to the relation between cortical convolution, anatomical connection and brain function.

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Proteomics and metabolomics in ageing research: from biomarkers to systems biology

Essays in Biochemistry ◽

10.1042/ebc20160083 ◽

2017 ◽

Vol 61 (3) ◽

pp. 379-388 ◽

Cited By ~ 26

Author(s):

Jessica M. Hoffman ◽

Yang Lyu ◽

Scott D. Pletcher ◽

Daniel E.L. Promislow

Keyword(s):

Risk Factor ◽

Systems Biology ◽

Human Populations ◽

Network Analyses ◽

Related Disease ◽

Ageing Research ◽

Age Related ◽

Wide Range ◽

Basic Biology ◽

The Impact

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations. Similarly, despite considerable effort, we have yet to identify reliable and reproducible ‘biomarkers’, which are predictors of one’s biological as opposed to chronological age. One challenge lies in the enormous mechanistic distance between genotype and downstream ageing phenotypes. Here, we consider the power of studying ‘endophenotypes’ in the context of ageing. Endophenotypes are the various molecular domains that exist at intermediate levels of organization between the genotype and phenotype. We focus our attention specifically on proteins and metabolites. Proteomic and metabolomic profiling has the potential to help identify the underlying causal mechanisms that link genotype to phenotype. We present a brief review of proteomics and metabolomics in ageing research with a focus on the potential of a systems biology and network-centric perspective in geroscience. While network analyses to study ageing utilizing proteomics and metabolomics are in their infancy, they may be the powerful model needed to discover underlying biological processes that influence natural variation in ageing, age-related disease, and longevity.

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Broccoli: combining phylogenetic and network analyses for orthology assignment

10.1101/2019.12.13.875831 ◽

2019 ◽

Cited By ~ 1

Author(s):

Romain Derelle ◽

Hervé Philippe ◽

John K. Colbourne

Keyword(s):

Learning Algorithm ◽

Phylogenetic Analyses ◽

Gene Clustering ◽

Comparative Genomic ◽

Orthology Assignment ◽

Bioinformatic Tools ◽

Network Analyses ◽

Benchmark Datasets ◽

Genomic Studies ◽

High Level

AbstractOrthology assignment is a key step of comparative genomic studies, for which many bioinformatic tools have been developed. However, all gene clustering pipelines are based on the analysis of protein distances, which are subject to many artefacts. In this paper we introduce Broccoli, a user-friendly pipeline designed to infer, with high precision, orthologous groups and pairs of proteins using a phylogeny-based approach. Briefly, Broccoli performs ultra-fast phylogenetic analyses on most proteins and builds a network of orthologous relationships. Orthologous groups are then identified from the network using a parameter-free machine learning algorithm. Broccoli is also able to detect chimeric proteins resulting from gene-fusion events and to assign these proteins to the corresponding orthologous groups. Tested on two benchmark datasets, Broccoli outperforms current orthology pipelines. In addition, Broccoli is scalable, with runtimes similar to those of recent distance-based pipelines. Given its high level of performance and efficiency, this new pipeline represents a suitable choice for comparative genomic studies.Broccoli is freely available at https://github.com/rderelle/Broccoli.

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AlzGPS: A Genome-wide Positioning Systems Platform to Catalyze Multi-omics for Alzheimer’s Therapeutic Discovery

10.1101/2020.09.17.302612 ◽

2020 ◽

Author(s):

Yadi Zhou ◽

Jiansong Fang ◽

Lynn Bekris ◽

Young Heon Kim ◽

Andrew A. Pieper ◽

...

Keyword(s):

Systems Biology ◽

Network Visualization ◽

Data Sets ◽

Omics Data ◽

Effective Prevention ◽

Positioning Systems ◽

Network Analyses ◽

Clinical Databases ◽

A Genome ◽

Disease Modules

AbstractBackgroundOver15 million family members and caregivers have expended $220 billion for care of patients with AD and other dementias, and the attrition rate for AD clinical trials (2002-2012) is estimated at 99.6%. While recent DNA/RNA sequencing and other multi-omics technologies have advanced the understanding of the biology and pathophysiology of AD, no effective disease-modifying or preventive therapies, for AD have emerged in the past two decades. A new approach to integration of the genome, transcriptome, proteome, and human interactome in the drug discovery and development process is essential for this endeavor.MethodsIn this study, we developed AlzGPS (Genome-wide Positioning Systems platform for Alzheimer’s Therapeutic Discovery, https://alzgps.lerner.ccf.org), a comprehensive systems biology tool to enable searching, visualizing, and analyzing multi-omics, various types of heterogeneous biological networks, and clinical databases for target identification and effective prevention and treatment of AD.ResultsVia AlzGPS: (1) we curated more than 100 AD multi-omics data sets capturing DNA, RNA, protein, and small molecules’ profiles underlying AD pathogenesis (e.g., early vs. late stage and tau vs. amyloid endophenotype); (2) we constructed endophenotype disease modules by incorporating multi-omics findings and human protein-protein interactome networks; (3) we identified repurposable drugs from ∼3,000 FDA approved/investigational drugs for AD using state-of-the-art network proximity analyses; (4) we curated 300 literature references for highly repurposable drugs; (5) we included information from over 200 ongoing AD clinicals noting drug mechanisms and primary drug targets, and linking them to our integrated multi-omics view for targets and network analyses results for the drugs; (6) we implemented a highly interactive web-interface for database browsing and network visualization.ConclusionsNetwork visualization enabled by the AlzGPS includes brain-specific neighborhood networks for genes-of-interest, endophenotype disease module networks for data sets-of-interest, and mechanism-of-action networks for drugs targeting disease modules. By virtue of combining systems pharmacology and network-based integrative analysis of multi-omics data, the AlzGPS offers actionable systems biology tools for accelerating therapeutic development in AD.

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ACE2 Expression is Increased in the Lungs of Patients with Comorbidities Associated with Severe COVID-19

10.1101/2020.03.21.20040261 ◽

2020 ◽

Cited By ~ 10

Author(s):

Bruna G.G. Pinto ◽

Antonio E.R. Oliveira ◽

Youvika Singh ◽

Leandro Jimenez ◽

Andre N A. Gonçalves ◽

...

Keyword(s):

Systems Biology ◽

Severe Acute Respiratory Syndrome ◽

Obstructive Lung Disease ◽

Human Lung ◽

Chronic Obstructive Lung Disease ◽

Host Cells ◽

Chronic Obstructive ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Network Analyses

AbstractThe pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) has resulted in several thousand deaths worldwide in just a few months. Patients who died from Coronavirus disease 2019 (COVID-19) often had comorbidities, such as hypertension, diabetes, and chronic obstructive lung disease. The angiotensin-converting enzyme 2 (ACE2) was identified as a crucial factor that facilitates SARS-CoV2 to bind and enter host cells. To date, no study has assessed the ACE2 expression in the lungs of patients with these diseases. Here, we analyzed over 700 lung transcriptome samples of patients with comorbidities associated with severe COVID-19 and found that ACE2 was highly expressed in these patients, compared to control individuals. This finding suggests that patients with such comorbidities may have higher chances of developing severe COVID-19. We also found other genes, such as RAB1A, that can be important for SARS-CoV-2 infection in the lung. Correlation and network analyses revealed many potential regulators of ACE2 in the human lung, including genes related to histone modifications, such as HAT1, HDAC2, and KDM5B. In fact, epigenetic marks found in ACE2 locus were compatible to with those promoted by KDM5B. Our systems biology approach offers a possible explanation for increase of COVID-19 severity in patients with certain comorbidities.

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Understanding Oriental Medicine Using a Systems Approach

Evidence-based Complementary and Alternative Medicine ◽

10.1093/ecam/nep037 ◽

2011 ◽

Vol 2011 ◽

pp. 1-3 ◽

Cited By ~ 1

Author(s):

Jong Yeol Kim ◽

Duong Duc Pham

Keyword(s):

Systems Biology ◽

Biological System ◽

Systems Approach ◽

Holistic Medicine ◽

Oriental Medicine ◽

High Level ◽

Problems Of Translation

Two international meetings, the International Physiome Symposium 2008 and the Workshop on Systems Biology (SB) and Oriental Medicine (OM), were held to discuss the most appropriate scientific tools to research OM. Participants agreed that since OM is holistic medicine it needs a systems approach such as SB. However, SB itself is still a long way from identifying the high-level organization processes in the biological system that might correlate with concepts in OM. As such, a modest goal of launching a project to examine the problems of translation and interpretation of OM concepts would be the first step.

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