The first systems analysis of the functioning of an organism was Claude Bernard's concept of the constancy of the internal environment (le milieu intérieur), since it implied the existence of control processes to achieve this. He can be regarded, therefore, as the first systems biologist. The new vogue for systems biology today is an important development, since it is time to complement reductionist molecular biology by integrative approaches. Claude Bernard foresaw that this would require the application of mathematics to biology. This aspect of Claude Bernard's work has been neglected by physiologists, which is why we are not as ready to contribute to the development of systems biology as we should be. In this paper, I outline some general principles that could form the basis of systems biology as a truly multilevel approach from a physiologist's standpoint. We need the insights obtained from higher‐level analysis in order to succeed even at the lower levels. The reason is that higher levels in biological systems impose boundary conditions on the lower levels. Without understanding those conditions and their effects, we will be seriously restricted in understanding the logic of living systems. The principles outlined are illustrated with examples from various aspects of physiology and biochemistry. Applying and developing these principles should form a major part of the future of physiology.

Claude Bernard, the first Systems Biologist, and the future of Physiology. The Paton Lecture 2007

Interpreting variants, especially noncoding ones, in the increasing number of personal genomes is challenging. We used patterns of polymorphisms in functionally annotated regions in 1092 humans to identify deleterious variants; then we experimentally validated candidates. We analyzed both coding and noncoding regions, with the former corroborating the latter. We found regions particularly sensitive to mutations ("ultrasensitive") and variants that are disruptive because of mechanistic effects on transcription-factor binding (that is, "motif-breakers"). We also found variants in regions with higher network centrality tend to be deleterious. Insertions and deletions followed a similar pattern to single-nucleotide variants, with some notable exceptions (e.g., certain deletions and enhancers). On the basis of these patterns, we developed a computational tool (FunSeq), whose application to ~90 cancer genomes reveals nearly a hundred candidate noncoding drivers.

Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

Complex biological systems and cellular networks may underlie most genotype to phenotype relationships. Here, we review basic concepts in network biology, discussing different types of interactome networks and the insights that can come from analyzing them. We elaborate on why interactome networks are important to consider in biology, how they can be mapped and integrated with each other, what global properties are starting to emerge from interactome network models, and how these properties may relate to human disease.

Interactome networks and human disease

Biological systems are in a constant process of innovation as an essential precondition to evolve. For this reason, the emergence of phenotypic variation is an inherent property of complex adaptive systems. Even though living systems acquire robustness to internal and external disturbances during the evolutionary process, pathological conditions entail impairments to their functionality. This is the rationale for studying biomedical issues according to the organizational properties of biological systems, with the aim of understanding the mechanisms of diseases. I first discuss the theoretical background that is suitable for the research included in this Thesis, such as my own interpretation of systems biology, the current theories about the origin of the biological modularity and some evolutionary considerations that concern in the genotype-phenotype relationships. In this section, I also argue the use and the development of integrative systems biology methods that should be addressed to evaluate disease modules: computational models (i.e. mathematical and network-based models) and other standardized efforts (ontologies and different databases with biological and biomedical data). Then, I enunciate the hypothesis and declare the objectives that motivated this research: i) mathematical modelling based on kinetic law formalism for studying the functional modularity of the metabolism; ii) the development of a workflow to integrate metabolic and kinetic data from different databases for metabolic modelling; iii) the evaluation of the functional coherence in phenotypic relationships between disease-causing genes by using network-based analysis; iv) the development of an integrative framework of biomedical information; v) the use of network medicine approaches to study the phenotypic and genotypic relationships in a heterogeneous group of patients with genetic syndromes. Finally, the results derived from the research carried out in this Thesis are included in the form of already published articles and manuscripts (either submitted or in preparation).

Systems Biology Approaches to Evaluate Disease Modularity

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

Armando Adolfo

Author Tools

Chat about Author

Papers

Systems Biology Approaches to Evaluate Disease Modularity