This document discusses systems biology and its goals of understanding how biological molecules interact and systems function as a whole. It covers:
1) Systems biology uses large datasets from "omics" experiments and computational models to understand complex biological interactions beyond individual molecules.
2) Pioneering work used microarrays to measure thousands of genes in serum-stimulated cells, finding over 500 changed in proliferation.
3) The field aims to discover emergent system properties and functions not evident from separate parts, like switches that change cell behavior.
Systems biology & Approaches of genomics and proteomicssonam786
This presentation provides the basic understanding of varous genomics and proteomics techniques.Systems biology studies life as a system .It includes the study of living system using various omic technologies .
I elaborated these slides for an introductory class on Network Medicine given at UPV (Valencia) in October 2017. The fundamental principle behind Network Medicine is that disease phenotypes emerge from genotypes via the network properties of interactions between the underlying biological components. These phenotypes are best conceptualized as consequences of perturbations to disease modules of the biological networks in the cell, whether at the node level (disease genes) or the link level (disease edgotypes). With the further analysis of drug-disease association and drug-target association data, one can investigate the effects - therapeutic and undesired - of the associated medication. Understanding the molecular level networks allows to understand the connections between different diseases and the effects of drugs designed to target them, paving the way for personalized treatments based on one's own interactome.
Introduction
Overview
Reductionist approach
Holistic approach
What is systems biology?
○ Advantages of Systems Biology
Tools of holistic approach
○ Proteomics, Transcriptomics and Metabolomics
Conclusion
References
Join us in Boston this coming Fall to attend Cambridge Healthtech Institute's (CHI) 2nd Annual FAST: Functional Analysis & Screening Technologies Congress on November 17-19, 2014 and meet with a community of 250+ biologists, screening managers, assay developers, engineers and pharmacologists dedicated to improving in vitro cell models and phenotypic screening to advance drug discovery and development at 6 conferences: Phenotypic Drug Discovery (Part I & II), Engineering Functional 3D Models, Screening and Functional Analysis of 3D Models, Organotypic Culture Models for Toxicology and Physiologically-Relevant Cellular Tumor Models for Drug Discovery. Delegates have the opportunity to share insights in interactive panel discussions and connect during networking breaks. View innovative technologies and scientific research revolutionizing early-stage drug discovery in the exhibit/poster hall.
Systems biology & Approaches of genomics and proteomicssonam786
This presentation provides the basic understanding of varous genomics and proteomics techniques.Systems biology studies life as a system .It includes the study of living system using various omic technologies .
I elaborated these slides for an introductory class on Network Medicine given at UPV (Valencia) in October 2017. The fundamental principle behind Network Medicine is that disease phenotypes emerge from genotypes via the network properties of interactions between the underlying biological components. These phenotypes are best conceptualized as consequences of perturbations to disease modules of the biological networks in the cell, whether at the node level (disease genes) or the link level (disease edgotypes). With the further analysis of drug-disease association and drug-target association data, one can investigate the effects - therapeutic and undesired - of the associated medication. Understanding the molecular level networks allows to understand the connections between different diseases and the effects of drugs designed to target them, paving the way for personalized treatments based on one's own interactome.
Introduction
Overview
Reductionist approach
Holistic approach
What is systems biology?
○ Advantages of Systems Biology
Tools of holistic approach
○ Proteomics, Transcriptomics and Metabolomics
Conclusion
References
Join us in Boston this coming Fall to attend Cambridge Healthtech Institute's (CHI) 2nd Annual FAST: Functional Analysis & Screening Technologies Congress on November 17-19, 2014 and meet with a community of 250+ biologists, screening managers, assay developers, engineers and pharmacologists dedicated to improving in vitro cell models and phenotypic screening to advance drug discovery and development at 6 conferences: Phenotypic Drug Discovery (Part I & II), Engineering Functional 3D Models, Screening and Functional Analysis of 3D Models, Organotypic Culture Models for Toxicology and Physiologically-Relevant Cellular Tumor Models for Drug Discovery. Delegates have the opportunity to share insights in interactive panel discussions and connect during networking breaks. View innovative technologies and scientific research revolutionizing early-stage drug discovery in the exhibit/poster hall.
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...Varij Nayan
“Organisms function in an integrated manner-our senses, our muscles, our metabolism and our minds work together seamlessly. But biologists have historically studied organisms part by part and celebrated the modern ability to study them molecule by molecule, gene by gene. Systems biology is critical science of future that seeks to understand the integration of the pieces to form biological
systems”
(David Baltimore, Nobel Laureate)
Perturbing The Interactome: Multi-Omics And Personalized Methods For Network ...Marc Santolini
In this talk, I will describe several recently developed methods to study disease perturbations through the lens of network science. First I will present evidence that one can accurately predict perturbation patterns from the topology of biological networks, even when lacking measurements on the kinetic parameters governing the dynamics of these interactions. Using 87 biochemical networks with experimentally measured kinetic parameters, we show that a knowledge of the network topology offers 65% to 80% accuracy in predicting the impact of perturbations. In other words, we can use the increasingly accurate topological models to approximate perturbation patterns, bypassing expensive kinetic constant measurement. These results open new avenues in modeling drug action, and in identifying drug targets relying on the human interactome only.
Then, I will present a novel approach to identify the collective impact of miRNAs in disease. Instead of focusing on the magnitude of miRNA differential expression, here we address the secondary consequences for the interactome. We developed the Impact of Differential Expression Across Layers (IDEAL), a network-based algorithm to prioritize disease-relevant miRNAs based on the central role of their targets in the molecular interactome. This method was used in the context of asthmatic Th2 inflammation and identified five Th2-related miRNAs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. This result offers novel approaches for therapeutic interventions.
Finally, I will present an investigation of the personalized gene expression responses when inducing hypertrophy and heart failure in 100+ strains of genetically distinct mice from the Hybrid Mouse Diversity Panel (HMDP). I will show that genes whose expression change significantly correlates with the severity of the disease are either up- or down-regulated across strains, and therefore missed by traditional population-wide analyses of differential gene expression. These uncovered personalised genes are enriched in human cardiac disease genes and form a dense co-regulated module strongly interacting with the cardiac hypertrophic signaling network in the human interactome, the set of molecular interactions in the cell. We validate our approach by showing that the knockdown of Hes1, predicted as a strong candidate, induces a dramatic reduction of hypertrophy by 80-90% in neonatal rat ventricular myocytes, demonstrating that individualized approaches are crucial to identify genes underlying complex diseases as well as to develop personalized therapies.
Introduction to graph databases and Neo4j for the bachelors student in Life sciences. Hands-on workshop for Neo4j and Cypher query language. The source of material for the hands-on training is: https://neo4j.com/graphacademy/online-training/introduction-to-neo4j/
In interactome, basically for interaction of proteins there is certain key elements requited, they are: Interactomics and Proteomics, Complementation groups, Modifier screens 1. Interactomics and Proteomics
Field of interactomics is concerned with interactions between genes or proteins. They can be genetic interactions, in which two genes are mainly involved in the same functional pathway (leading to a particular phenotype), or physical interactions, in which there is direct physical contact between two proteins (or between protein and DNA) (Janga et al.,2008). 2. Complementation groups Using forward saturation genetics, one may recover several independent mutants with the same (or similar) phenotype (Hernández et al., 2007). There are two possibilities: a) Mutations are in the same gene b) Mutations are in different genes involved in the same pathway. Scenario
(b) Can be tested genetically with a complementation test:
Cross two homozygous mutants (samples) and observe heterozygous offspring phenotypes(samples)
Mutations in the same gene will not complement
offspring have mutant phenotype
Mutations in different genes will complement
offspring have wild
Type phenotype
Do pairwise crosses for all mutants to identify complementation groups
Typically each complementation group represents a different gene
If many mutations are recovered in the same genes, this implies saturation
Presentation for Network Biology SIG 2013 by Thomas Kelder, Bioinformatics Scientist at TNO in The Netherlands. “Functional Network Signatures Link Anti-diabetic Interventions with Disease Parameters”
Presentation for NetBio SIG 2013 by Martina Kutmon, PhD Researcher in the BiGCaT Bioinformatics Dept at the University of Maastricht in the Netherlands. “Building Biological Regulatory Networks in Cytoscape Using CyTargetLinker”
ANALYSIS OF PROTEIN MICROARRAY DATA USING DATA MININGijbbjournal
Latest progress in biology, medical science, bioinformatics, and biotechnology has become important and
tremendous amounts of biodata that demands in-depth analysis. On the other hand, recent progress in data
mining research has led to the development of numerous efficient and scalable methods for mining
interesting patterns in large databases. This paper bridge the two fields, data mining and bioinformatics
for successful mining of biological data. Microarrays constitute a new platform which allows the discovery
and characterization of proteins.
Protein protein interaction, functional proteomicsKAUSHAL SAHU
IntroductionTypes of Protein-protein interactionsEffects of Protein-Protein InteractionsProtein-Protein Interaction Identification Methods :- Experimental (In vivo) Yeast two hybrid system- Experimental (In vitro) Co-immunoprecipitation, ChIP, Affinity Blotting, Protein Probing - Computational (In silico) Database of interacting proteins, VisANT etc.
ConclusionReferences
WHAT IS BIOINFORMATICS?
Computational Biology/Bioinformatics is the application of computer sciences and allied technologies to answer the questions of Biologists, about the mysteries of life. It has evolved to serve as the bridge between:
Observations (data) in diverse biologically-related disciplines and
The derivations of understanding (information)
APPLICATIONS OF BIOINFORMATICS
Computer Aided Drug Design
Microarray Bioinformatics
Proteomics
Genomics
Biological Databases
Phylogenetics
Systems Biology
Interactomics, Integromics to Systems Biology: Next Animal Biotechnology Fron...Varij Nayan
“Organisms function in an integrated manner-our senses, our muscles, our metabolism and our minds work together seamlessly. But biologists have historically studied organisms part by part and celebrated the modern ability to study them molecule by molecule, gene by gene. Systems biology is critical science of future that seeks to understand the integration of the pieces to form biological
systems”
(David Baltimore, Nobel Laureate)
Perturbing The Interactome: Multi-Omics And Personalized Methods For Network ...Marc Santolini
In this talk, I will describe several recently developed methods to study disease perturbations through the lens of network science. First I will present evidence that one can accurately predict perturbation patterns from the topology of biological networks, even when lacking measurements on the kinetic parameters governing the dynamics of these interactions. Using 87 biochemical networks with experimentally measured kinetic parameters, we show that a knowledge of the network topology offers 65% to 80% accuracy in predicting the impact of perturbations. In other words, we can use the increasingly accurate topological models to approximate perturbation patterns, bypassing expensive kinetic constant measurement. These results open new avenues in modeling drug action, and in identifying drug targets relying on the human interactome only.
Then, I will present a novel approach to identify the collective impact of miRNAs in disease. Instead of focusing on the magnitude of miRNA differential expression, here we address the secondary consequences for the interactome. We developed the Impact of Differential Expression Across Layers (IDEAL), a network-based algorithm to prioritize disease-relevant miRNAs based on the central role of their targets in the molecular interactome. This method was used in the context of asthmatic Th2 inflammation and identified five Th2-related miRNAs (mir27b, mir206, mir106b, mir203, and mir23b) whose antagonization led to a sharp reduction of the Th2 phenotype. This result offers novel approaches for therapeutic interventions.
Finally, I will present an investigation of the personalized gene expression responses when inducing hypertrophy and heart failure in 100+ strains of genetically distinct mice from the Hybrid Mouse Diversity Panel (HMDP). I will show that genes whose expression change significantly correlates with the severity of the disease are either up- or down-regulated across strains, and therefore missed by traditional population-wide analyses of differential gene expression. These uncovered personalised genes are enriched in human cardiac disease genes and form a dense co-regulated module strongly interacting with the cardiac hypertrophic signaling network in the human interactome, the set of molecular interactions in the cell. We validate our approach by showing that the knockdown of Hes1, predicted as a strong candidate, induces a dramatic reduction of hypertrophy by 80-90% in neonatal rat ventricular myocytes, demonstrating that individualized approaches are crucial to identify genes underlying complex diseases as well as to develop personalized therapies.
Introduction to graph databases and Neo4j for the bachelors student in Life sciences. Hands-on workshop for Neo4j and Cypher query language. The source of material for the hands-on training is: https://neo4j.com/graphacademy/online-training/introduction-to-neo4j/
In interactome, basically for interaction of proteins there is certain key elements requited, they are: Interactomics and Proteomics, Complementation groups, Modifier screens 1. Interactomics and Proteomics
Field of interactomics is concerned with interactions between genes or proteins. They can be genetic interactions, in which two genes are mainly involved in the same functional pathway (leading to a particular phenotype), or physical interactions, in which there is direct physical contact between two proteins (or between protein and DNA) (Janga et al.,2008). 2. Complementation groups Using forward saturation genetics, one may recover several independent mutants with the same (or similar) phenotype (Hernández et al., 2007). There are two possibilities: a) Mutations are in the same gene b) Mutations are in different genes involved in the same pathway. Scenario
(b) Can be tested genetically with a complementation test:
Cross two homozygous mutants (samples) and observe heterozygous offspring phenotypes(samples)
Mutations in the same gene will not complement
offspring have mutant phenotype
Mutations in different genes will complement
offspring have wild
Type phenotype
Do pairwise crosses for all mutants to identify complementation groups
Typically each complementation group represents a different gene
If many mutations are recovered in the same genes, this implies saturation
Presentation for Network Biology SIG 2013 by Thomas Kelder, Bioinformatics Scientist at TNO in The Netherlands. “Functional Network Signatures Link Anti-diabetic Interventions with Disease Parameters”
Presentation for NetBio SIG 2013 by Martina Kutmon, PhD Researcher in the BiGCaT Bioinformatics Dept at the University of Maastricht in the Netherlands. “Building Biological Regulatory Networks in Cytoscape Using CyTargetLinker”
ANALYSIS OF PROTEIN MICROARRAY DATA USING DATA MININGijbbjournal
Latest progress in biology, medical science, bioinformatics, and biotechnology has become important and
tremendous amounts of biodata that demands in-depth analysis. On the other hand, recent progress in data
mining research has led to the development of numerous efficient and scalable methods for mining
interesting patterns in large databases. This paper bridge the two fields, data mining and bioinformatics
for successful mining of biological data. Microarrays constitute a new platform which allows the discovery
and characterization of proteins.
Protein protein interaction, functional proteomicsKAUSHAL SAHU
IntroductionTypes of Protein-protein interactionsEffects of Protein-Protein InteractionsProtein-Protein Interaction Identification Methods :- Experimental (In vivo) Yeast two hybrid system- Experimental (In vitro) Co-immunoprecipitation, ChIP, Affinity Blotting, Protein Probing - Computational (In silico) Database of interacting proteins, VisANT etc.
ConclusionReferences
WHAT IS BIOINFORMATICS?
Computational Biology/Bioinformatics is the application of computer sciences and allied technologies to answer the questions of Biologists, about the mysteries of life. It has evolved to serve as the bridge between:
Observations (data) in diverse biologically-related disciplines and
The derivations of understanding (information)
APPLICATIONS OF BIOINFORMATICS
Computer Aided Drug Design
Microarray Bioinformatics
Proteomics
Genomics
Biological Databases
Phylogenetics
Systems Biology
Presentation summarising the 2013 ICSB conference in Copenhagen, a requirement of James Hutton Institute Visits Abroad funding. Presented at the Cellular and Molecular Sciences seminar series.
insilico protein structure prediction and and structure analysis and its type which are commonly used in dry lab. docking is a procedure in which two protein,or protein to ligand binding intrection analysis by software tools.
National Resource for Networks Biology's TR&D Theme 1: In this theme, we will develop a series of tools and methodologies for conducting differential analyses of biological networks perturbed under multiple conditions. The novel algorithmic methodologies enable us to make use of high-throughput proteomic level data to recover biological networks under specific biological perturbations. The software tools developed in this project enable researchers to further predict, analyze, and visualize the effects of these perturbations and alterations, while enabling researchers to aggregate additional information regarding the known roles of the involved interactions and their participants.
Study of Membrane Transport for Protein Filtration Using Artificial Neural Ne...IJERDJOURNAL
ABSTRACT: Artificial Neural Networks (ANNs) are nonlinear mapping structures which functions same as human brain. Modeling can be made stronger especially while the underlying data relationship is not known. ANNs may recognize and learn inter-related patterns between input data sets and related target values. After training, ANNs may be utilized to judge the output of new independent input data. Thus ANNs are used best for the modeling of membrane processes, like ultra filtration and microfiltration. This allows us to judge the permeate flux and membrane rejection as functions of process variables. The aim is modeling of membrane transport for protein filtration is to analyze membrane systems by means of ANNs. To analyze this different ANNs are developed with the help of Mat lab. [1a][9]
Community Finding with Applications on Phylogenetic Networks [Extended Abstract]Luís Rita
[Master Thesis Extended Abstract]
With the advent of high-throughput sequencing methods, new ways of visualizing and analyzing increasingly amounts of data are needed. Although some software already exist, they do not scale well or require advanced skills to be useful in phylogenetics.
The aim of this thesis was to implement three community finding algorithms – Louvain, Infomap and Layered Label Propagation (LLP); to benchmark them using two synthetic networks – Girvan-Newman (GN) and Lancichinetti-Fortunato-Radicchi (LFR); to test them in real networks, particularly, in one derived from a Staphylococcus aureus MLST dataset; to compare visualization frameworks – Cytoscape.js and D3.js, and, finally, to make it all available online (mscthesis.herokuapp.com).
Louvain, Infomap and LLP were implemented in JavaScript. Unless otherwise stated, next conclusions are valid for GN and LFR. In terms of speed, Louvain outperformed all others. Considering accuracy, in networks with well-defined communities, Louvain was the most accurate. For higher mixing, LLP was the best. Contrarily to weakly mixed, it is advantageous to increase the resolution parameter in highly mixed GN. In LFR, higher resolution decreases the accuracy of detection, independently of the mixing parameter. The increase of the average node degree enhanced partitioning accuracy and suggested detection by chance was minimized. It is computationally more intensive to generate GN with higher mixing or average degree, using the algorithm developed in the thesis or the LFR implementation. In S. aureus network, Louvain was the fastest and the most accurate in detecting the clusters of seven groups of strains directly evolved from the common ancestor.
National Resource for Networks Biology's TR&D Theme 3: Although networks have been very useful for representing molecular interactions and mechanisms, network diagrams do not visually resemble the contents of cells. Rather, the cell involves a multi-scale hierarchy of components – proteins are subunits of protein complexes which, in turn, are parts of pathways, biological processes, organelles, cells, tissues, and so on. In this technology research project, we will pursue methods that move Network Biology towards such hierarchical, multi-scale views of cell structure and function.
Statistical Analysis based Hypothesis Testing Method in Biological Knowledge ...ijcsa
The correlation and interactions among different biological entities comprise the biological system. Although already revealed interactions contribute to the understanding of different existing systems, researchers face many questions everyday regarding inter-relationships among entities. Their queries have potential role in exploring new relations which may open up a new area of investigation. In this paper, we introduce a text mining based method for answering the biological queries in terms of statistical computation such that researchers can come up with new knowledge discovery. It facilitates user to submit their query in natural linguistic form which can be treated as hypothesis. Our proposed approach analyzes the hypothesis and measures the p-value of the hypothesis with respect to the existing literature. Based on the measured value, the system either accepts or rejects the hypothesis from statistical point of view. Moreover, even it does not find any direct relationship among the entities of the hypothesis, it presents a network to give an integral overview of all the entities through which the entities might be related. This is also congenial for the researchers to widen their view and thus think of new hypothesis for further investigation. It assists researcher to get a quantitative evaluation of their assumptions such that they can reach a logical conclusion and thus aids in relevant re-searches of biological knowledge discovery. The system also provides the researchers a graphical interactive interface to submit their hypothesis for assessment in a more convenient way.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
How to Split Bills in the Odoo 17 POS ModuleCeline George
Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
The Art Pastor's Guide to Sabbath | Steve ThomasonSteve Thomason
What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
Students, digital devices and success - Andreas Schleicher - 27 May 2024..pptxEduSkills OECD
Andreas Schleicher presents at the OECD webinar ‘Digital devices in schools: detrimental distraction or secret to success?’ on 27 May 2024. The presentation was based on findings from PISA 2022 results and the webinar helped launch the PISA in Focus ‘Managing screen time: How to protect and equip students against distraction’ https://www.oecd-ilibrary.org/education/managing-screen-time_7c225af4-en and the OECD Education Policy Perspective ‘Students, digital devices and success’ can be found here - https://oe.cd/il/5yV
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
1. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
Lecture 1
1
The title of this lecture is 'Systems biology for medicine' and it deals with getting and organizing the
big data in such a way that we can extract from them diagnostically and therapeutically relevant
information.
We will start with explanation what are the parts of biological systems and how they assemble
together in order to perform certain physiological functions.
2
You probably have this kind of a small kitchen aid machine and you know how it functions.
3
Depending on cutting piece inserted into machine you can cut the carrot on few different ways.
After some practice you'll be able to predict how carrot will look like if you use one or another
cutting piece.
In general, we can say - the function of this machine is to cut soft objects into predictable shapes.
4
It is easy to guess the function of simple machines, but if machine is built out of many parts it
becomes harder and harder.
How likely is that you would recognize snow blower on this image?
5
The more complex system gets it’s harder to predict all the possible functions performed by it.
2. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
For example, the human body consist out of approximately 200 different types of cells and each of
this types is built from different number of molecules, which can be a couple of dozen or hundreds of
thousands - and they (cells) perform slightly different functions.
6
Systems biology is scientific discipline which had arisen after emergence of experimental methods
able to collect and analyse a big number of data at the same time, especially driven by emergence of
microarray techniques.
Systems biology is trying to understand how molecules mutually interact and associates together to
give rise to subcellular machinery that form functional units capable of actions that are needed for
cellular, tissue or organ level physiological functions.
The definition is given by Ravi Iyengar, one of the pioneers at the field of systems biology.
7
Up to emergence of microarray techniques scientists dealt with individual molecules and the most
often they investigated binary interactions between molecules.
Good example is discovery of haemoglobin structure and function which took 25 years.
The four peptide chains associates in order to bind, transfer and release 4 molecules of oxygen under
specific physiological conditions.
How it happens was concluded by using X-ray diffraction and protein crystallography.
Haemoglobin is crystallized and position of each atom is determined from diffraction of X-rays after
passing through crystals.
John Kendrew & Max Perutz got the Nobel price at 1962 for their discovery.
3. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
Their technique is now used worldwide to determine the structure of large molecules, especially to
determine active site on enzymes and interaction between enzyme and substrate.
8
Systems biology is the molecular level of physiology.
We can explain that by looking at the insulin signalling pathway.
After injecting insulin at the blood stream of animal we can measure various physiological effects -
increased glucose uptake in skeletal muscle and fat tissue, increased glycogen synthesis in muscle,
decreased hepatic glucose production and decreased lipolysis in adipocytes.
In general, we can say that purpose of insulin signalling is to enhance glucose cellular uptake and to
stimulate cell metabolism.
If we look at the molecular level - we see the flow of information from outside of the cell to certain
intracellular metabolic pathways which is executed through a number of molecular interactions.
9
Molecular interactions obey the law of mass action and proceed till chemical equilibrium.
It means that each molecular interaction can be presented as mathematical equation.
We have to know initial concentrations of ligands/substrates and receptors/enzymes as well as rates
of forward and reverse reactions.
If we know all initial parameters we could compute how product of enzyme reactions is formed with
respect to time.
4. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
10
Entire signalling pathway could be written as a series of ordinary differential equations.
We can mathematically present each molecular interaction so that product of one reaction is used in
following reaction, pathways can finish with end product or come back onto receptor.
Also, entire signalling pathway could be integrated in computational model.
11
Stepwise discovering of individual interactions is so called bottom-up approach.
Such approach is widely used in 20th century and resulted with seminal understanding of biological
processes.
The bottom-up approach uses hypothesis driven studies.
The success of this approach is manifested through the number of Nobel prizes awarded for the
discoveries of individual molecules and their interactions in signalling pathways.
12
Each discovery was further contributing to complexity.
Pathways gradually rose to networks.
In order to predict outcome of network functioning, system biology is using computational models.
13
Up to now we can conclude:
5. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
1. Systems biology builds on molecular biology, biochemistry and cell biology and uses already
collected knowledge about biological interactions.
2. Systems biology integrates existing knowledge from many experiments in computational
models .
Purpose for using computational models is to find functions coming out from complex
interactions not predicted by looking at individual components (e. g. presence of switch in a
signaling network, robustness…)
14
A switch in a signalling network was described for the first time in Bhalla and Iyengar's paper.
The authors were investigating mutually interacting pathways PLCγ-PKC and Ras-Raf-MAPK using in
parallel experimental proof and computational model.
Both pathways start with EGF receptor and after ligand binds to receptor it causes rise in activity of
MAPK which gradually decreases.
Just and only if levels of ligand EFG rise above 5 nM, activity of MAPK do not come back to baseline
levels, but remain high and cell starts to divide.
The switch is based on integration of two pathways into joined network and its purpose is to switch
the cell from one mode of operation into another - from resting state to division.
15
Another behaviour which is noticed after computing entire networks was existence of positive and
negative feedback loops.
6. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
Presence of positive and negative regulators enables cell to maintain same level of physiological
functions under wide range of external stimuli what we recognize as flexibility and robustness.
16
Besides building computational models, field of systems biology heavily relies on experiments that
collect a large number of data at the same time, measuring many molecular entities at once, like in
micro-array studies.
Such a type of studies is so called top-down approach and is not base on initial hypothesis, but we
should rather say that hypothesis get generated out of big data.
17
One of the first papers using the big data was investigating fibroblast response to serum.
Microarrays used for this study contained probes for 8613 human genes and had been measuring
9996 elements at the same time.
Library of cDNA molecules from serum deprived cells was labelled by Cy3, while library of cDNA from
serum exposed cells was labelled by Cy5.
Overlap of two equally represented probes, yellow in colour, was reflecting lack of change, while
appearance of red or green spot was interpreted as difference caused by induction.
Total number of 517 genes changed expression after serum exposure and contributed to change of
cellular operation- from resting state to proliferation.
18
Molecules commonly used for generating the big data are
- DNA sequances represented as DNA probes for genes or probes for non-coding sequences
- variuous classes of RNAs
7. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
- proteins
- cellular lipids
- and small molecules produced by metabolism - so called metabolites.
19
Gathering the big data is usually recognized by suffix 'omics'.
Omics is any experimental approach which simultaneously measures many individual entities at the
same time point.
Omics type of experiments use at least two sets of big data which were collected in different time
points or under different conditions or has any other difference measurable by statistical method.
Representative examples of omic studies are genomics which collects data about genes involved in
physiological processes, proteomics which results in data about co-expressed genes and
metabolomics which list all metabolites produces by cellular machinery at the given time point.
20
In order to find relevant data from a large database, data should be organized according to certain
principles.
Bioinformatics is a scientific discipline that uses mostly mathematical tools in organizing the big data
what enables further comparison or search.
A large number of databases is already publicly available, for example GEO (results of mRNA
profiling), Target Scan (data about microRNA), Swiss-Prot (a large protein base), OMIM (the list and
description of disease genes), DbGAP (results of Genome-wide association studies).
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There are two possible ways of using data from a big data base: the first is to generate list of entities
that are statistically co-related in the same base(e.g. all co-expressed proteins at starvation)
8. “A cross-border region where rivers connect, not divide” –
Interreg V-A Hungary-Croatia Co-operation Programme 2014-2020
the second is generating list of statistically co-related entities between different bases – e.g. all
expressed mRNAs in Down syndrome.
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In conclusion:
1. Systems biology builds on biochemistry, molecular biology and cell biology
2. Systems biology uses experiments designed in OMICs style.
3. The further analysis of collected big data uses statistical methods, bioinformatics approach and
different types of modelling.
4. The main goal of systems biology is to discover hidden mechanisms and functions that derive from
the system as a whole and which cannot be detected by observing individual parts.
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At the end - I hope that you can guess what is the function of machine from this image in the field of
systems biology.