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Andres Kriete

Publications and source records attributed to Andres Kriete.

11 recordsLinked to original sources
PubMed2006

Systems approaches to the networks of aging.

The aging of an organism is the result of complex changes in structure and function of molecules, cells, tissues, and whole body systems. To increase our understanding of how aging works, we have to analyze and integrate quantitative evidence from multiple levels of biological organization. Here, we define a broader conceptual framework for a quantitative, computational systems biology approach to aging. Initially, we consider fractal supply networks that give rise to scaling laws relating body mass, metabolism and lifespan. This approach provides a top-down view of constrained cellular processes. Concomitantly, multi-omics data generation build such a framework from the bottom-up, using modeling strategies to identify key pathways and their physiological capacity. Multiscale spatio-temporal representations finally connect molecular processes with structural organization. As aging manifests on a systems level, it emerges as a highly networked process regulated through feedback loops between levels of biological organization.

Aging↗
PubMed2006

Biomarkers of aging: combinatorial or systems model?

Systemwide functional and structural changes caused by the aging process encourage the implementation of new bioinformatics search strategies for markers of aging. Combinatorial biomarkers should be particularly favored, as they can quantify processes on multiple levels of biological organization and overcome an otherwise limited ability to access heterogeneities in populations. An even more challenging but rational approach is the development of systems biology models to describe molecular pathways and key networks mechanistically as they relate to age. Such reverse engineered models not only indicate critical and diagnostic components (that is, potential biomarkers) but also should be able to predict the progression of aging through computer simulation.

Aging↗
PubMed2006

Bridging biological scales by state-space analysis and modeling using molecular, tissue cytometric and physiological data.

Combining data streams across different levels of biological organization such as molecular, cellular, and physiological responses support to a system-wide view in biology. Recently, an unbiased analysis of tissues that provides data-rich descriptors of tissue architecture, cell types, and cell states has become available. As tissues are centrally located in the biological hierarchy, these advancements give rise to a new class of state variables that are critical to elucidate both underlying cellular, molecular and emergent physiological properties. Concepts to statistically identify, correlate, and model relationships across scales are introduced, which rely on a state-space matrix derived by multi-omics data aggregation.

Computational Biology↗
PubMed2006

System-wide analysis of hepatotoxicological responses: tissomics is key.

BACKGROUND: Combining diverse data streams across different levels of biological observation, such as molecular, cellular, and clinical chemistry responses, support a system-wide diagnostic approach. Recent progress in slide-based cytometry contributes to the development of tissomics, a high-throughput and high-content phenotyping methodology that provides data-rich profiles of cellular heterogeneity in tissues enabling correlative statistical treatments over multiple scales of biological hierarchies. METHODS: Phenotypical data are covariants that can be used as biomarkers to identify relevant candidate genes by associating initiating molecular events with phenotypical changes and adverse outcomes. We introduce a procedure of combined statistical and analytical tools to identify and visualize such associations for nonpooled entities. The new utility is applied to a time-controlled, low-dose toxicological study including a control and two xenobiotic compounds. RESULTS: An integrated analysis identified specific molecular and phenotypical biomarkers, which support the classification of animals in the absence of any visual indicators from pathology readings. DISCUSSION: The introduction of controlled perturbations to tissues provides a prototypical setting to develop a sensitive, systems-based analysis methodology suitable for a broader range of biomedical applications.

Animals↗
PubMed2005

Phenotypical enrichment strategies for microarray data analysis applied in a type II diabetes study.

Combining results from gene microarrays, clinical chemistry, and quantitative tissue histomorphology in an integrated bioinformatics setting enables prioritization of gene families as well as individual genes in a type II diabetes animal study. This new methodology takes advantage of a time-controlled mouse study as the animals progress from a normal phenotype to that of type II diabetes. Profiles from different levels of the biological hierarchy of unpooled entities provide an encompassing, system-wide view of biological changes. Here, phenotypic changes on the tissue-structural and physiological level are used as statistical covariants to enrich the gene expression analysis, suggesting correlative processes between gene expression and phenotype unlocked by multi-sample comparisons. We apply correlative and gene set enrichment procedures and compare the results to differential analysis to identify molecular markers. Evaluation based on ontological classifications proves changes in prioritization of disease-related genes that would have been overlooked by conventional gene expression analyses strategies.

Animals↗
PubMed2005

Micro-CT of the human lung: imaging of alveoli and virtual endoscopy of an alveolar duct in a normal lung and in a lung with centrilobular emphysema--initial observations.

The appearance of human lung parenchyma at the structural level of alveoli was investigated by the use of micro-computed tomography (CT). Approval for use of autopsy lungs was given by the head of the pathology institute of the university, in accordance with the requirements of the State Ministry of Science and Arts and without the need for institutional review board approval. Two human lungs (one normal lung and one lung with centrilobular emphysema of a mild to moderate degree) were inflated and fixed with hot formalin vapor. Lung specimens excised from the superior segment of the left lower lobe (B6) were stained with silver nitrate in a vacuum and investigated at a volume of interest of 4 mm for each side with a voxel size of 14 mum. Normal-size and enlarged alveoli became visible. A three-dimensional reconstruction of the terminal airspaces made virtual endoscopy of the alveolar ducts possible.

Aged↗
PubMed2004

A digital reference model of the human bronchial tree.

In-vitro preparations of the human lung combined with high-resolution tomography can be used to derive precise models of the human lung. To develop an abstract graph representation, specially adapted image processing algorithms were applied to segment and delineate the bronchi. The graph thus obtained contains topological information about spatial coordinates, connectivities, diameters and branching angles of 1453 bronchi up to the 17th Horsfield order. The graph was analyzed for statistical and fractal properties and was compared with current models. Results indicate a model that exhibits asymmetry and multifractal properties. This newly established reference model is an important step forward in geometrical accuracy of the bronchial tree representation that will improve both analysis of lung images in clinical imaging and the realism of functional simulations.

Adult↗
PubMed2003

Combined histomorphometric and gene-expression profiling applied to toxicology.

We have developed a unique methodology for the combined analysis of histomorphometric and gene-expression profiles amenable to intensive data mining and multisample comparison for a comprehensive approach to toxicology. This hybrid technology, termed extensible morphometric relational gene-expression analysis (EMeRGE), is applied in a toxicological study of time-varied vehicle- and carbon-tetrachloride (CCl4)-treated rats, and demonstrates correlations between specific genes and tissue structures that can augment interpretation of biological observations and diagnosis.

Animals↗