References of "Galas, David J. 40000219"
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See detailComplexity of Networks II: The Set Complexity of Edge-Colored Graphs
Ignac, Tomasz UL; Sakhanenko, N. A.; Galas, David J. UL

in Complexity (2012), 17(5), 23-36

We previously introduced the concept of “set-complexity”, based on a context-dependent measure of information, and used this concept to describe the complexity of gene interaction networks. In the ... [more ▼]

We previously introduced the concept of “set-complexity”, based on a context-dependent measure of information, and used this concept to describe the complexity of gene interaction networks. In the previous paper in this series we analyzed the set-complexity of binary graphs. Here we extend this analysis to graphs with multi-colored edges that more closely match biological structures like the gene interaction networks. All highly complex graphs by this measure exhibit a modular structure. A principal result of this work is that for the most complex graphs of a given size the number of edge colors is equal to the number of “modules” of the graph. Complete multipartite graphs (CMGs) are defined and analyzed, and the relation between complexity and structure of these graphs is examined in detail. We establish that the mutual information between any two nodes in a CMG can be fully expressed in terms of entropy, and present an explicit expression for the set complexity of CMGs (Theorem 3). An algorithm for generating highly complex graphs from CMGs is described. We establish several theorems relating these concepts and connecting complex graphs with a variety of practical network properties. In exploring the relation between symmetry and complexity we use the idea of a similarity matrix and its spectrum for highly complex graphs. [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 detailRELATION BETWEEN THE SET-COMPLEXITY OF A GRAPH AND ITS STRUCTURE
Ignac, Tomasz UL; Galas, David J. UL; Sakhanenko, Nikita

in Proceedings of the 8th International Workshop on Computational Systems Biology (2011)

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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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