The Systems Biology of COVID-19 and the SARS-CoV-2 virus. The class will build a foundation that includes the emergence of complexity, simple biological subsystems, their reductionist and equivalent toy and organ-chip models, and the measurements required to specify model architecture and parameters. Applications to biology, physiology, medicine, chemical and biological defense, pharmacology, drug discovery, and toxicology. UGrad: PHYS 240 01 and BME 290B; Grad: PHYS 326 and BME 395C.
Sunday, January 18, 2015
SysBio15 Asgn_5A_Class_05_Article_07_2015_01_20
Systems Biology Dimensions and Challenges: Read
Article 07 S. Huang and J. Wikswo. Dimensions of systems biology. In:
Reviews of Physiology, Biochemistry and Pharmacology, edited by S. G.
Amara, E. Bamberg, T. Gudermann, S. C. Hebert, R. Jahn, W. J. Lederer,
R. Lill, A. Miyajima, and S. Offermanns, 2006, p. 81-104. Post a PCRC on the Blog
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Cameron Togrye
ReplyDeleteAsgn_5A / Systems Biology Dimensions and Challenges
0.Knew: The number of genes in humans (approximately 25,000) is comparably the same size as the number of genes in much 'simpler' organisms such as the plant Arabidopsis thaliana. Perhaps this can be made up for by a proportionally higher amount of post translational modification, or perhaps the answer lies in more complex interactions between these biomolecules.
1. Learned: Cell's exist in what Waddington described as an "epigenetic lanscape" whose energetically favorable 'valleys' determined the stable-cell types cells could develop into depending on their external conditions.
2. Pressing: In the article, it suggests that there are perhaps 'features' in organisms which did not arise from the functional optimization of adaptation. What are some examples of such features? How do we know that they aren't simply in process of optimization? Also, at what level of abstraction do models cease to be useful? Abstraction in physics works perfectly because of how homogeneous the various materials worked with are, whereas two genes, proteins, cells or even two tissues can vary widely, and thus are seemingly difficult to abstract. Isn't biology already an emergent phenomenon in itself?
3. Presentation: The epigenetic lanscape
4. I found myself hoping that this article would pin down a comprehensive, explicit definition of systems biology as I often ask myself if I could actually define it. Is it the complexity of the things it describes which makes it so hard to define?
Kendra Oliver
ReplyDeleteAsgn_5A / Systems Biology Dimensions and Challenges
Dimensions of systems biology
0. Knew: There has been a huge amount of information from genomic and proteomic data over the last decade of research. Reductionist approach to biology has yielded a wide array of knowledge but there is a lack on re-construction from those finding. A constructionist approach has the potential to show the wider applicability of the reductionist findings.
1. Learned: Thinking of systems biology as a return to organismal physiology. “Analysis of entirety rather than the entireness of analysis”
A. Molecular complexity: Integrating molecules and pathways to genome-wide networks “horizontal integration”
B. Structural complexity: Transcending many size-scales, organelles-cell-tissues-organs-organism ‘vertical integration”
C. Temporal complexity: Transcending many time scales
D. Abstraction and emergence: modeling system-level “emergent” features
E. Algorithmic complexity: Understanding information coding and computation by the biological medium and developing models that stimulate biological systems
2. Pressing: For a true systems biology approach do you need to apply all of these complexities simultaneously? How do you choice which approach to use?
3. Presentation: Discussing the types of questions that can be addressed with each type of complexity
4. Thoughts: Has there been further divisions within system biology discipline besides splitting it into mentioned divisions? Has there been division based on organ system?
James Pino
ReplyDeleteAssignment 5A
0: Knew: The broad term of systems biology.
1:Learned: The dimensions of SB. The concept of Turing-complete. The fine detail of mutliscale modeling and its challenges, both temporally and spatially. # of human genes is same order of magnitude of primitive organism. Complexity could arise from hacks in the code of life rather than optimal design
2:Pressing: How do we know when we reach the optimal level between abstraction and detail? If we view a living organism as a computing machine then did god rest while life was compiled on the 7th day?
3:Presentation: Dimensions of system biology. Examples of each and why they exist.
4:Thoughts: The complexity continues to grow. Zooming in and out from multiple angles is a great way to view SB and where it is going.
Selene van der Walt
ReplyDeleteAssignment 5A
0. Knew: That ‘systems biology’ is a frequently used but definitely not clearly defined term. I also understood the importance of the whole organism approach (away from reductionist thought) that systems biology focuses on. Also knew about the extensive categorization of genes and proteins by “omics” sciences.
1. Learned: about the benefits of defining the five dimensions of systems biology: molecular complexity, structural complexity, temporal complexity, abstraction and emergence, and algorithmic complexity.
2. Pressing ?: Is it possible to use a reverse engineering method to define the complex networks of a system without using experiments to discover individual interactions? Can the field of bioinformatics keep up with systems biology, so we are able to process the increasingly large data sets systems biologists are creating? What does it mean that systems biology is a ‘discovery science’ rather than a ‘hypothesis driven science’?
3. Presentation: The concept of living systems having a deep ‘scale space’
4. Thoughts: I think it’s interesting that our knowledge that there is a finite number of genes and proteins (though it is very large) just fuels our desire to identify every single one of them. I also found the comments equating systems biology to ‘network biology’ helpful in clarifying what exactly systems biology as a field hopes to achieve.
Arman Chowdhury
ReplyDeleteAssignment 5A
0. Knew: There are limitations of “reductionism” in molecular biology. “A living system is a physical system that computes its own development and homeostasis in response to external perturbations”
1. Learned: Five dimensional space to understand systems biology constitutes of: (1) molecular complexity; (2) structural complexity; (3) temporal complexity; (4) abstraction and emergence; and (5) algorithmic complexity. A system as a whole is the product of high-order combinatorial multiplication, not a simple linear summation of its individual functional parts. “Organisms are replete with features that may represent frozen historical accidents and local optima fixed by evolution” (86-87). If molecular biology represents “software”, structural complexity represents “hardware” in biological systems.
2. Pressing ?: Do biological clocks exist in cellular level (temporal oscillation in the cell division cycle) or systems level (circadian rhythm), or both? Where do phenomena like the “circadian rhythm” originate from? Are emergent properties seen only in complex organisms, like higher mammals?
3. Presentation: Clear subheadings make it easy to understand what dimensional space author is talking about.
4. Thoughts: The section on abstraction and emergent properties was especially interesting to me, since it is fascinating that emergent phenomena can only be understood in higher levels and is irreducible into lower components of functions – the idea of the system being a product of high-order combinatorial multiplication, rather than linear summation. The idea of bit-by-bit simulation of biological phenomena is also exciting – maybe then we can truly understand human physiology, and even higher phenomena like consciousness.
Kate Jones
ReplyDeleteAssignment 5A Article 7
0. Knew: I knew that the driving force for the emergence of systems biology was the need to overcome the limitations of reductionism in molecular biology and that a key aspect of systems biology is to analyze the whole rather than the individual parts of the system to understand how the system works. We had also discussed the emergent properties of systems are integral to the study of systems biology.
1. Learned: I learned that systems biology is difficult to really define, but the complexity that it attempts to simplify can be broken down into 5 dimensions that often are related: molecular complexity, structural complexity, temporal complexity, abstraction and emergence, and algorithmic complexity.
2. Pressing ?: Do the five dimensions represent different areas of systems biology? Also, when taking the temporal complexity into account, how do we account for characteristic irregularities such as an irregular heartbeat?
3. Presentation: Taking some time to work through table 1 would be a concise way to make sure we all understand the different dimensions, how they work together, what projects related to the dimension attempt to accomplish, and the challenges researchers working with these dimensions still face.
4. Thoughts: I really liked the examples under each subheading. It helped me see what types of projects fall under the name systems biology. Because systems biology is difficult to define, and that is an important point of the article, the examples were important for me to better define systems biology.
Tim Lee
ReplyDeleteAsgn_5A
0. Knew: Basic ideas about systems biology: a multidisciplinary approach to understanding the complexities of biology as multiple complex systems come together.
1. Learned: A breakdown of systems biology into five specific dimensions: molecular complexity, structural complexity, temporal complexity, abstraction and emergence, and algorithmic complexity. I learned that each of the dimensions contain an irreducible element at the higher levels of complexity that cannot be simply defined by the lower levels of complexities that constitute it.
2. Presssing: What are some ways in which we can find other dimensions of systems biology? It seems to me that each dimension is so complex that they even begin to overlap each other (structural and temporal). Is there a classification that can encompass some of the defined dimensions together?
3. Presentation: A detailed overview of systems biology and its major dimensions.
4. Thoughts: It's crazy to me how at the higher complexity levels, it's almost as if we're trying to discover science all over again since we can't linearly build up the lower levels of complexities that we know to explain things at the higher level. I just assumed at our current progression of technology and knowledge, we'd be able to explain everything by functions of what we already know but now it seems like we have many years, decades, even centuries, to observe and explain all of the phenomena biology has to offer.
Cami Johnson
ReplyDeleteAssignment 5A: Article 7
0. Knew: That systems biology sought to understand the complexity of the whole organism, in contrast to the reductionist approach of analyzing each part, but that it is also a slightly ill-defined term
1. Learned: Systems biology can be divided into five dimensions of organism complexity in order to better define the field and its importance. 1) Molecular complexity: understanding how genes and proteins interact (a "wiring diagram" so to speak). 2) Structural complexity: understanding the hierarchy of structures and their properties. 3) Temporal complexity: understanding the dynamic and time variant behavior of biological processes. 4) Abstraction and emergence: understanding how different parts come together to perform a function which isn't immediately obvious from each individual component. 5) Algorithmic complexity: understanding the information coding of the organism, developing models to stimulate biological processes, and accepting the limitations of said models.
2. Pressing ?: How does behavior or environment fit into these five dimensions? I understand the importance of abstraction, but how do you know where to draw the line between too simple and too complex?
3. Presentation: The article broke systems biology down into five main areas of focus in order to better define the fields.
4. Thoughts: I was glad to read more about the general idea of systems biology because I have found myself a couple times wondering exactly how to define it. I thought the different dimensions were really interesting, as well as the concept that understanding every individual part doesn't equate to understanding the whole and how it works.
Juan Gnecco
ReplyDeleteAsgn 5A
Knew: Foundation and need for systems biology as a way to intergrate what we "know" in the age of omics and the complexity of this problem.
Learned: The five dimensions of systems biology that can help define phyisiological parts. Organ on chips aid the stuctural complexity dimension. The discovery vs hypothesis driven mentality is not true - big picture idea.
2. Pressing; How do we scale an organ that is continuously changing i.e. every 28 days in terms of number of cells, sizes and distances?
3: Presentation: how systems biology can be interpreted as a required analysis and application of the complexity of a system based on what we know.
4. Thoughts: this is a very complicated field and I personally conceived it as a theoretical investigation based on mathematical models (i.e. dimension 4), but it is not that and is derived from actual experiments.
Chuck Herring
ReplyDeleteAsgn 5A
0. Knew: General knowledge about systems biology.
1. Learned: The complexity of systems biology and the details about the challenges of investigating biology from this perspective.
2. Pressing; What role will advanced statistical methods and machine learning play in systems biology's future?
3: Presentation: An overview of systems biology.
4. Thoughts: As complexity grows reproducibility of experiments can suffer, how will this affect the reporting process?
Shuaipeng "Jimmy" Zhang
ReplyDeleteAssignment 5A
0. Knew: Basic definition of systems biology. The concepts of reductionist and constructionist biology, and emergent properties.
1. Learned: The 5 dimensions of systems biology mentioned in the article: molecular complexity, structural complexity, temporal complexity, abstraction and emergence, algorithmic complexity.
2. Pressing ?: The article mentioned "dissipative structures", which are quasi-stationary, ordered structures that take up (nonthermic) energy and produce entropy to main order. What are some examples (if any) of these structures? At which level of complexity do emergent properties begin to appear (cellular or organismal)?
3. Presentation: The classification of systems biology into 5 dimensions.
4. Thoughts: This article emphasized the complexity of systems biology and how truly encompassing it is. And in order to understand an organism, emphasis must be placed on the interactions at different levels of complexity instead of the individual parts.
Mark Vander Roest
ReplyDeleteAssignment 5A
0) Knew: The basics of biological complexity, especially relating to molecular, structural, and temporal complexity. Previous reductionist strategies for biology including genomics/proteomics and how they have contributed and fallen short in contributing to systems biology.
1) Learned: Much more about the concept of emergence, abstraction, and algorithmic complexity. The concept of viewing cells or even tissues as mathematically described black boxes rather than hyper-complex combinations of multiple molecules in which each physical interaction is described (higher abstraction).
2) Pressing ?: The section on molecular complexity discusses the contribution of various omics approaches, the need for network understanding and wiring diagrams, etc. only to shoot them down as a reversion of reductionism, then to come back and say that they're warranted and necessary. What's the deal with that and is there a more correct approach?
3) Presentation: The various levels of complexity that exist in systems biology and the mindset that one must have to reach an understanding of the subject.
4) Thoughts: The section describing basins of attraction reminded me of gravity wells in the youtube videos of spacetime, and made me further realize the need for a totally outside approach to biology if a good appreciation of systems biology can occur.
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ReplyDeleteJPW
Priyanka Ravichandran
ReplyDeleteAssignment 5A
0. Knew - systems biology is hard to define; it is necessary to create a “network map” of the genome to see and understand all the interactions
1. Learned - what the five dimensions of systems biology are, how each is measured and the challenges of each
2. Pressing - how can we develop tools that will accurately and completely collect the data that encompass all five dimensions?
3. Presentation - gave a detailed definition of systems biology by explaining the 5 dimensions
4. Thoughts - I thought Table 1 was a good summary of the whole article. I liked how the article used real examples of phenomena in the body to illustrate these dimensions.