scholarly journals Separating the Drivers from the Driven: Integrative Network and Pathway Approaches Aid Identification of Disease Biomarkers from High-Throughput Data

2010 ◽  
Vol 28 (4) ◽  
pp. 253-266 ◽  
Author(s):  
Jason E. McDermott ◽  
Michelle Costa ◽  
Derek Janszen ◽  
Mudita Singhal ◽  
Susan C. Tilton

The recent advances in high-throughput data acquisition have driven a revolution in the study of human disease and determination of molecular biomarkers of disease states. It has become increasingly clear that many of the most important human diseases arise as the result of a complex interplay between several factors including environmental factors, such as exposure to toxins or pathogens, diet, lifestyle, and the genetics of the individual patient. Recent research has begun to describe these factors in the context of networks which describe relationships between biological components, such as genes, proteins and metabolites, and have made progress towards the understanding of disease as a dysfunction of the entire system, rather than, for example, mutations in single genes. We provide a summary of some of the recent work in this area, focusing on how the integration of different kinds of complementary data, and analysis of biological networks and pathways can lead to discovery of robust, specific and useful biomarkers of disease and how these methods can help shed light on the mechanisms and etiology of the diseases being studied.

2003 ◽  
Vol 62 (4) ◽  
pp. 777-781 ◽  
Author(s):  
Rosemary A. Richardson ◽  
H. Isobel M. Davidson

Common to both acute and chronic disease are disturbances in energy homeostasis, which are evidenced by quantitative and qualitative changes in dietary intake and increased energy expenditure. Negative energy balance results in loss of fat and lean tissue. The management of patients with metabolically-active disease appears to be simple; it would involve the provision of sufficient energy to promote tissue accretion. However, two fundamental issues serve to prevent nutritional demands in disease being met. The determination of appropriate energy requirements relies on predictive formulae. While equations have been developed for critically-ill populations, accurate energy prescribing in the acute setting is uncommon. Only 25–32% of the patients have energy intakes within 10% of their requirements. Clearly, the variation in energy expenditure has led to difficulties in accurately defining the energy needs of the individual. Second, the acute inflammatory response initiated by the host can have profound effects on ingestive behaviour, but this area is poorly understood by practising clinicians. For example, nutritional targets have been set for specific disease states, i.e. pancreatitis 105–147 KJ (25–35 kcal)/kg; chronic liver disease 147–168 kj (35–40 kcl)/kg, but given the alterations in gut physiology that accompany the acute-phase response, targets are unlikely to be met. In cancer cachexia attenuation of the inflammatory response using eicosapentaenoic acid results in improved nutritional intake and status. This strategy poses an attractive proposition in the quest to define nutritional support as a clinically-effective treatment modality in other disorders.


F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2524 ◽  
Author(s):  
Gabriele Tosadori ◽  
Ivan Bestvina ◽  
Fausto Spoto ◽  
Carlo Laudanna ◽  
Giovanni Scardoni

Biological networks are becoming a fundamental tool for the investigation of high-throughput data in several fields of biology and biotechnology. With the increasing amount of information, network-based models are gaining more and more interest and new techniques are required in order to mine the information and to validate the results. To fill the validation gap we present an app, for the Cytoscape platform, which aims at creating randomised networks and randomising existing, real networks. Since there is a lack of tools that allow performing such operations, our app aims at enabling researchers to exploit different, well known random network models that could be used as a benchmark for validating real, biological datasets. We also propose a novel methodology for creating random weighted networks, i.e. the multiplication algorithm, starting from real, quantitative data. Finally, the app provides a statistical tool that compares real versus randomly computed attributes, in order to validate the numerical findings. In summary, our app aims at creating a standardised methodology for the validation of the results in the context of the Cytoscape platform.


2012 ◽  
Vol 6 (1) ◽  
pp. 54 ◽  
Author(s):  
Florian Martin ◽  
Ty M Thomson ◽  
Alain Sewer ◽  
David A Drubin ◽  
Carole Mathis ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2524 ◽  
Author(s):  
Gabriele Tosadori ◽  
Ivan Bestvina ◽  
Fausto Spoto ◽  
Carlo Laudanna ◽  
Giovanni Scardoni

Biological networks are becoming a fundamental tool for the investigation of high-throughput data in several fields of biology and biotechnology. With the increasing amount of information, network-based models are gaining more and more interest and new techniques are required in order to mine the information and to validate the results. We have developed an app for the Cytoscape platform which allows the creation of randomized networks and the randomization of existing, real networks. Since there is a lack of tools for generating and randomizing networks, our app helps researchers to exploit different, well known random network models which could be used as a benchmark for validating real datasets. We also propose a novel methodology for creating random weighted networks starting from experimental data. Finally the app provides a statistical tool which compares real versus random attributes, in order to validate all the numerical findings. In summary, our app aims at creating a standardised methodology for the validation of the results in the context of the Cytoscape platform.


F1000Research ◽  
2017 ◽  
Vol 5 ◽  
pp. 2524 ◽  
Author(s):  
Gabriele Tosadori ◽  
Ivan Bestvina ◽  
Fausto Spoto ◽  
Carlo Laudanna ◽  
Giovanni Scardoni

Biological networks are becoming a fundamental tool for the investigation of high-throughput data in several fields of biology and biotechnology. With the increasing amount of information, network-based models are gaining more and more interest and new techniques are required in order to mine the information and to validate the results. To fill the validation gap we present an app, for the Cytoscape platform, which aims at creating randomised networks and randomising existing, real networks. Since there is a lack of tools that allow performing such operations, our app aims at enabling researchers to exploit different, well known random network models that could be used as a benchmark for validating real, biological datasets. We also propose a novel methodology for creating random weighted networks, i.e. the multiplication algorithm, starting from real, quantitative data. Finally, the app provides a statistical tool that compares real versus randomly computed attributes, in order to validate the numerical findings. In summary, our app aims at creating a standardised methodology for the validation of the results in the context of the Cytoscape platform.


Author(s):  
Tomás C. Moyano ◽  
Elena A. Vidal ◽  
Orlando Contreras-López ◽  
Rodrigo A. Gutiérrez

2015 ◽  
Author(s):  
Urszula Czerwinska ◽  
Laurence Calzone ◽  
Emmanuel Barillot ◽  
Andrei Zinovyev

Visualization and analysis of molecular profiling data together with biological networks are able to provide new mechanistical insights into biological functions. Currently, high-throughput data are usually visualized on top of predefined network layouts which are not always adapted to a given data analysis task. We developed a Cytoscape app which allows to construct biological network layouts based on the data from molecular profiles imported as values of nodes attributes. DeDaL is a Cytoscape 3.0 app which uses linear and non-linear algorithms of dimension reduction to produce data-driven network layouts based on multidimensional data (typically gene expression). DeDaL implements several data pre-processing and layout post-processing steps such as continuous morphing between two arbitrary network layouts and aligning one network layout with respect to another one by rotating and mirroring. Combining these possibilities facilitates creating insightful network layouts representing both structural network features and the correlation patterns in multivariate data. DeDaL is the first method allowing to construct biological network layouts from high-throughput data. DeDaL is freely available for downloading together with step-by-step tutorial at http://bioinfo-out.curie.fr/projects/dedal/.


Author(s):  
Benjamin Pickard

Schizophrenia is a common mental illness resulting from a complex interplay of genetic and environmental risk factors. Establishing its primary molecular and cellular aetiopathologies has proved difficult. However, this is a vital step towards the rational development of useful disease biomarkers and new therapeutic strategies. The advent and large-scale application of genomic, transcriptomic, proteomic and metabolomic technologies are generating data sets required to achieve this goal. This discovery phase, typified by its objective and hypothesis-free approach, is described in the first part of the review. The accumulating biological information, when viewed as a whole, reveals a number of biological process and subcellular locations that contribute to schizophrenia causation. The data also show that each technique targets different aspects of central nervous system function in the disease state. In the second part of the review, key schizophrenia candidate genes are discussed more fully. Two higher-order processes – adult neurogenesis and inflammation – that appear to have pathological relevance are also described in detail. Finally, three areas where progress would have a large impact on schizophrenia biology are discussed: deducing the causes of schizophrenia in the individual, explaining the phenomenon of cross-disorder risk factors, and distinguishing causative disease factors from those that are reactive or compensatory.


1970 ◽  
Vol 6 (1) ◽  
pp. 184-193
Author(s):  
Ольга Віговська

У статті теоретично обґрунтовано феномен конструктивного самозбереження особистості як ознаки самоактуалізації, розкриття власного потенціалу і побудови перспективи розвитку особистості та емпірично виявлено ознаки психологічної детермінації домінуючого інстинкту у конструктивній самореалізації жінок з різним соціальним статусом. Зазначено, що проблема самозбереження асоціюється з особливостями прояву інстинкту самозбереження людини, але потреби вищого порядку зумовлюють соціальну природу її поведінки, яка локалізована у найвищій точці самореалізації. Теоретично обгрунтовано, що самореалізація визначає тенденцію раціональної організації життя людини та проявляється у її почутті задоволеністю життям. З’ясовано, що психологічну основу конструктивного самозбереження становлять індивідуально-типологічні характеристики людини, які відображають психофізіологічні та психосоціальні резерви самореалізації особистості. Розроблена програма емпіричного дослідження, а також комплекс використаних методів математичної обробки результатів дослідження дає змогу конкретизувати психологічний зміст детермінації домінуючого інстинкту у конструктивній самореалізації жінок вікового діапазону 35-45 років та з різним соціальним статусом. У жінок, які виховують проблемну (хвору) дитину, домінує інстинкт "егофільного типу", що виражається у їх надмірному егоцентризмі і супроводжується низькими показниками самоактуалізації, на відміну від досліджуваних жінок, які виховують здорових дітей і у яких на фоні вираженої тенденції до самоактуалізації домінує базовий інстинкт "дослідницького типу" та "лібертофільного типу". This article theoretically proves constructive phenomenon of self identity as signs of self-disclosure own potential and prospects of development of individual construction. In addition, it empirically showes signs of psychological determination of the dominant instinct in a constructive self-determination of women with different social statuses. It was noted that the issue of self-preservation is associated with the peculiarities of manifestation of self-preservation instinct of man, but it needs higher-order cause social nature of the behavior that is localized at the highest point of self-realization. It theorized that self-realization determines the trend of rational organization of human life and manifests itself in its sense of life satisfaction. It was found that the psychological basis of constructive self-preservation of the individual make individually-typological characteristics of a person that reflect physiological and psychosocial reserves of self-realization. The developed program of empirical research, as well as the methods used complex mathematical processing of results of research allows to specify the content of the psychological determination of the dominant instinct of constructive self-realization а women age range of 35-45 years and with different social status. Women who bring up the problem child dominates the instinct of self-preservation, which is reflected in their excessive self-centeredness, and is accompanied by low levels of self-actualization, as opposed to the study of women who are raising healthy children and that against the backdrop of a pronounced tendency to self-actualization, dominated by basic instinct "research type" and "independent type."


Author(s):  
Rafea Shareef Dhanoon

The close relations between Turkey and Libya are still on the rise, and this was evident through Turkish support at all levels of the internationally recognized government of Al-Sarraj winner. The Memorandum of Understanding signed between Turkey and Libya on 27 / November 2019, in the areas of security and military cooperation and the determination of areas of influence revealed The navy, the extent of the historical close relationship between Ankara and Tripoli, just as the Turkish President Erdogan wanted to deliver a message to the West and other regional parties after the signing of the Memorandum of Understanding, that Turkey has a non-negotiable sovereign right to define the maritime spheres of influence and that this right stems from international law. In light of these tracks, we will shed light on the orientations of Turkish policy towards Libya after the February 2011 revolution, by defining the determinants of those trends and examining the most important obstacles in the march of Turkish policy towards Libya.


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