References of "Hood, Leroy 40000310"
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See detailNetwork analysis for systems biology
Chaiboonchoe, A.; Jurkowski, Wiktor UL; Pellet, J. et al

in Prokop, Aleš; Csukás (Eds.) Springer book in Systems Biology, Vol.1: Systems Biology:, Integrative Biology and Simulation Tools (2013)

Network analysis is an essential component of systems biology approaches toward understanding the molecular and cellular interactions underlying biological systems functionalities and their perturbations ... [more ▼]

Network analysis is an essential component of systems biology approaches toward understanding the molecular and cellular interactions underlying biological systems functionalities and their perturbations in disease. Regulatory and signalling pathways, which involve DNA, RNA proteins and metabolites as key elements, coordinate most aspects of cellular functioning. Cellular processes, which are dependent on the structure and dynamics of gene regulatory networks, can be studied by employing a network representation of molecular interactions. In this chapter we describe several types of networks and how combination of different analytic approaches can be used to study diseases. We provide a list of selected tools for visualization and network analysis. We introduce protein-protein interaction networks, gene regulatory networks, signalling networks and metabolic networks. We then define concepts underlying network representation of cellular processes and molecular interactions. We finally discuss how the level of accuracy in inferring functional relationships influences the choice of methods applied for the analysis of a particular network type. [less ▲]

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See detailFunctional Genomics, Proteomics, Metabolomics and Bioinformatics for Systems Biology
Ballereau, S.; Glaab, Enrico UL; Kolodkin, Alexey UL et al

in Prokop, Ales; Csukás, Bela (Eds.) Systems Biology: Integrative Biology and Simulation Tools (2013)

This chapter introduces systems biology, its context, aims, concepts and strategies. It then describes approaches and methods used for collection of high-dimensional structural and functional genomics ... [more ▼]

This chapter introduces systems biology, its context, aims, concepts and strategies. It then describes approaches and methods used for collection of high-dimensional structural and functional genomics data, including epigenomics, transcriptomics, proteomics, metabolomics and lipidomics, and how recent technological advances in these fields have moved the bottleneck from data production to data analysis and bioinformatics. Finally, the most advanced mathematical and computational methods used for clustering, feature selection, prediction analysis, text mining and pathway analysis in functional genomics and systems biology are reviewed and discussed in the context of use cases. [less ▲]

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See detailComputational infrastructures for data and knowledge management in systems biology
Georgatos, Fotis UL; Ballereau, S.; Pellet, J. et al

in Prokop, Ales; Csukás, Bela (Eds.) Systems Biology: Integrative Biology and Simulation Tools (2013)

The volume, complexity and heterogeneity of data originating from high throughput functional genomics technologies have created challenges and opportunities for Information Technology (IT) departments ... [more ▼]

The volume, complexity and heterogeneity of data originating from high throughput functional genomics technologies have created challenges and opportunities for Information Technology (IT) departments. These increased demands have also led to increasing costs for IT infrastructure such as necessary computing power and storage devices, as well as further costs for manpower effort, required for maintenance. This chapter describes some of the challenges for computational analysis infrastructure, including bottlenecks and most pressing needs that have to be addressed to effectively support the development of systems biology and its application in medicine. [less ▲]

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See detailRevolutionizing medicine in the 21(st) century through systems approaches
Hood, Leroy UL; Balling, Rudi UL; Auffray, Charles

in Biotechnology Journal (2012), 7(8), 937-1054

Personalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to ... [more ▼]

Personalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to reflect the enormous dimensionality of this new medicine that will be predictive, preventive, personalized, and participatory-a vision of medicine we have termed P4 medicine. This reflects a paradigm change in how medicine will be practiced that is revolutionary rather than evolutionary. P4 medicine arises from the confluence of a systems approach to medicine and from the digitalization of medicine that creates the large data sets necessary to deal with the complexities of disease. We predict that systems approaches will empower the transition from conventional reactive medical practice to a more proactive P4 medicine focused on wellness, and will reverse the escalating costs of drug development an will have enormous social and economic benefits. Our vision for P4 medicine in 10 years is that each patient will be associated with a virtual data cloud of billions of data points and that we will have the information technology for healthcare to reduce this enormous data dimensionality to simple hypotheses about health and/or disease for each individual. These data will be multi-scale across all levels of biological organization and extremely heterogeneous in type - this enormous amount of data represents a striking signal-to-noise (S/N) challenge. The key to dealing with this S/N challenge is to take a "holistic systems approach" to disease as we will discuss in this article. [less ▲]

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See detailChromosomal haplotypes by genetic phasing of human families
Roach, Jared C.; Glusman, Gustavo; Hubley, Robert et al

in American Journal of Human Genetics (2011), 89(3), 382-397

Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable ... [more ▼]

Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromosomal positions and specific meioses. We demonstrate this process of genetic phasing on two families each with four children. We generate haplotypes for all of the children and their parents; these haplotypes span all genotyped positions, including rare variants. Misassignments of phase between variants (switch errors) are nearly absent. Our algorithm can also produce multimegabase haplotypes for nuclear families with just two children and can handle families with missing individuals. We implement our algorithm in a suite of software scripts (Haploscribe). Haplotypes and family genome sequences will become increasingly important for personalized medicine and for fundamental biology. [less ▲]

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See detailCandidate mutations for early-onset lung cancer by family genome sequencing
Simeonidis, Vangelis UL; Roach, Jared; Brunkow, Mary et al

Poster (2011, July)

Early-onset lung cancer has been studied as a rare, but distinct, sub-type of lung cancer. Genome-wide association studies (GWAS) have linked several genes with this form of malignancy. We sequenced the ... [more ▼]

Early-onset lung cancer has been studied as a rare, but distinct, sub-type of lung cancer. Genome-wide association studies (GWAS) have linked several genes with this form of malignancy. We sequenced the genomes of a family quartet in which one of the offspring was diagnosed with early-onset lung cancer at about 48 years of age. The family has a history of heavy smoking and the father had in the past been diagnosed with head and neck cancer. The DNA source was blood, which leads us to concentrate our analysis on Mendelian inheritance models. To make the inheritance pattern explicit, we establish the parental origin of the offspring’s genomes through phasing of their chromosomes. This helps identify whether mutations in the proband came from the father or the mother. More than 18 million sequence variants were initially identified in the proband through comparison to the hg19 reference genome. We reduce this list to fewer than 200 potentially functional variants (e.g. single nucleotide variations and short indels) present in the genomes of the proband and at least one parent, by applying a series of filters. We refine the list of candidate mutations further by comparison to gene candidates from GWAS studies and genes that are mutated in lung cancer tissue as recorded by The Cancer Genome Atlas. The results of our analysis are discussed and conclusions about possible causative mutations for early-onset lung cancer are drawn. [less ▲]

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See detailMicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia
Moussay, Etienne; Wang, Kai; Cho, Ji-Hoon et al

in Proceedings of the National Academy of Sciences of the United States of America (2011), 108(16), 6573-6578

Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and can provide ... [more ▼]

Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and can provide some relevant insights into cancer biology. Recent studies have suggested improvements in detecting malignancies by the use of specific extracellular microRNAs (miRNAs) in plasma. In chronic lymphocytic leukemia (CLL), an incurable hematologic disorder, sensitive, early, and noninvasive diagnosis and better disease classification would be very useful for more effective therapies. We show here that circulating miRNAs can be sensitive biomarkers for CLL, because certain extracellular miRNAs are present in CLL patient plasma at levels significantly different from healthy controls and from patients affected by other hematologic malignancies. The levels of several of these circulating miRNAs also displayed significant differences between zeta-associated protein 70 (ZAP-70)(+) and ZAP-70(-) CLL. We also determined that the level of circulating miR-20a correlates reliably with diagnosis-to-treatment time. Network analysis of our data, suggests a regulatory network associated with BCL2 and ZAP-70 expression in CLL. This hypothesis suggests the possibility of using the levels of specific miRNAs in plasma to detect CLL and to determine the ZAP-70 status. [less ▲]

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See detailSystems medicine and integrated care to combat chronic noncommunicable diseases
Bousquet, J.; Anto, J. M.; Sterk, P. J. et al

in Genome Medicine (2011), 3(7), 43-47

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic ... [more ▼]

We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems. [less ▲]

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See detailDiseases as network perturbations
del Sol Mesa, Antonio UL; Balling, Rudi UL; Hood, Leroy UL et al

in Current Opinion in Biotechnology (2010), 21(4), 566-571

The tremendous amount of the data obtained from the study of complex biological systems changes our view on the pathogenesis of human diseases. Instead of looking at individual components of biological ... [more ▼]

The tremendous amount of the data obtained from the study of complex biological systems changes our view on the pathogenesis of human diseases. Instead of looking at individual components of biological processes, we focus our attention more on the interaction and dynamics of biological systems. A network representation and analysis of the physiology and pathophysiology of biological systems is an effective way to study their complex behavior. Specific perturbations can trigger cascades of failures, which lead to the malfunctioning of cellular networks and as a result to the development of specific diseases. In this review we discuss recent developments in the field of disease network analysis and highlight some of the topics and views that we think are important for understanding network-based disease mechanisms. [less ▲]

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