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Lluch and Baliga: Discussion

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Lluch and Baliga: Discussion
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no more general questions yes I have a question for or my but before I ask my question I have to clear up some misunderstandings that may appear as I ask my question so first of all I'm a
strong proponent of using models and biology even though I feel close to what knitting Baliga expressed on the use of models and that these models that are dedicated to a morning a certain phenomenon for certain purpose in a multi-state away as needed for the to express the biological phenomena and the second misunderstanding I want to clear that I have very much admire the work that is done at crg and I think it's very useful now I can come to my question basically what I understand so a bit of a caricature to make myself clear what I understand is that you have brought a lot of information that was useful to better calibrate the car and coverage model the wholesale model mycoplasma so that you spend some time on that discussing with these guys sending their time explaining the data and so on I'd like to know if you save any time on your side's using their model for your foot to guide your own experiments yeah that's the final proportion of the Horsham wildest ride which I so happy Tasha food for predicting or facilitating the work in the lab and we have an still use it we are currently putting more effort in having me off you want to for doing that so so check shall we say then that their model would be perfect if it were a scalable model like the Emperor China you know you who asked requested because it is powerful men and requested a scale one map of his own Empire so that in some sense you have a scale model because you're working on my plasma they don't have this moment yet because they are using a virtual copy of it which is imperfect with such a whole model we are good only at the time it makes hundred percent correct predictions which will never happen in my opinion and be useless until then I don't think that it cannot be used at the state that it's normal but our goal is tied to copy and paste with manner to thank you reproduce simulations more alienated to the application for you
wanna know in this sense so we want to do a bit of a defined media to work tomorrow we need to make an early model of their families that is not currently implemented in the halls and Mar to make all the concept that content of the different components of the media and see for changing media capital to grow so at the end is depending on the application of the world if to the model they improve this have you have to do
and how to you you want to use it and I'm not saying that the correlation that we have continued for some prediction line a vital energy we expect on the side with professionals lower you can you can treat this modification and if you want to walk in death understudy for work an engineer the medium and every childhood education degree zero that I can do so we added we are still developing use for these proposals your comment I'll make a comment I think it's not just room for 450 G if someone claims that mathematical modeling and simulation makes a correct prediction he misunderstands so disappear because it only takes consequences from assumptions and therefore let's vary up I never would claim to make a prediction of this kind I give you an example so we have studied a lot of compassion theory and from modeling simulation which user a lot but if you ever see the mother and you want to predict what happens in the morning it's still possible because your knowledge is not there and the same thing is for population ma populations of microorganisms are saving but you should use it main I'm very happy if I can improve an experiment that's and therefore experimental design is a very important part which may have not just biologists chemists wherever you reduce your use your costs at your time I agree the basis of all is the knowledge and also the inter connection between the people the modeling experts and experimental is persuading that the way you have agreed to a great team and will click on operators and hopefully one day we can merge all alpha prepared system and we have a question we want to produce something and you make invitations a network the network dynamic because you optimize all zones of structure there is missing mathematics which can do it it's we try to look-look a lot of that it is the best tools needed to solve this from mathematical I think you're right on the second place I've been told where you may not have numerical methods is when you go across scales so when you go from this is something different we have to discuss that what you mean by that but it keeps your network trust the network wrong there is not a very little good systems reduction network for some optimization it's a challenge to mathematics okay in reading the your question all day bottom top applause I think that the characterization of different components in the system in this case you know since then is good because i canna promoter studies we know we're not cool identify which are assignments or which are the best combinations of depends send instead of the structure or a level of sequence that we could use for expressing genes also by the transcriptome analysis and assigning different conditions we could identify a possible regulators and hawaii are they unwilling to even buy recognitions so itself information that can be applied for the design of genetic circuit so I am finally we're cool right to the moment of implementing all this information in a host and model then we will expect that by a sign different combination to keep this information at different levels we could like when in silico design is what we would like and a silikal design of this circuit before testing in the lab so will be our goal and hopefully one day we can question in terms of with the systems modeling one question I had it it was kind of struck by the central the example that was given where you have two organisms to try to get them to adapt to each other but how much I guess maybe my question is how much how much can you on how much how far away are we from being able to model systems evolving right so in other words not a static system but if you're talking us entropy these work as a doctor each other conditions and so on but then you like a sister yeah yeah modeling the evolution is very difficult because when the genetic change pad it's difficult to make predictions of the body consequence of trajan what you can do however is it could in context of the metabolic fluxes and the dependencies of the tow system you could find the constraints for how that system could he set up your way that you can have the right kinds of inputs so that they have optimal behavior you can do that but if there's a notation in a regulated network that could improve that that you got if not impossible to make a prediction is do what that might be might have a general based on the principle you might say that for example if I were to project this onto evolution of an organism that is going back and forth between nitrification and denitrification I would say a regulatory networks around denitrification enzymes are disrupted that type of fluctuation is better likely to proceed or evolve because regulation is not required of those genes which is counterintuitive but is but it's the principle of this level so also my concern is boot and proposal she's good but the problem is that we don't know how our limitations would have finally to the function of the different earrings so in the evolution process at the end you first need to know which is been part of the mutations to know which will be there they happen does it which is their selection so that's the main limitation to use the mothers for predicting which may be the revolution
comes a little bit to the aggression which we have before comment we have to go from seat yourselves to population that's enough scaling which is terrible you can imagine you measure so much processes and very secular sources stuff and a sequel cell population you Carol three this this is criticizes importance because it's too huge space at the app of nations in Europe but they make predictions about populations but this is always the other way around experimental it's the other way around even easier to actually measure populations and get data on populations and it's much more difficult to get it on scene you asked the question easy call from information on level on a molecular level in a Cell the Experian average salary I'll give you that event of experimental data the end it's easier to obtain when you are not doing amies we are taking into consideration all the only population of a week we still don't know exactly which is the impact of having different cells into the population and also is not the same the condition Tamara that the conditions in their burial condition didn't touch your procedure when shall we tell them that is anything escaping that it's ready thank you for the times we just write those kennel taxes for a populated take the information what's inside so cell happens and it's very complicated it's not satisfactory for the biology that's the first step was another question these are points of shopping with mathematician so you know you are you have shown a certain certain part regulatory network so my question for me do you think in fact that the organism is completely described by this huge graphic with all these relationships because when you from the latter point of view with the regular network like that you can do everything so you can put ten more notes so this means that these pictures for example like the popular one of the crib cycles with 1000 ft pappy you can do nice calendars are nice posters what is information that this is there so at the end you realize when do we choose mycoplasma because looks very simple it has a very low number of zooms and the respect that you can add rice properly the different element unconfident i'll see what is a cross talk between the different biological process but at the end you realize that there is a ladder there is a lot of complexity because a level of regulatory network is not only the transcription factors because the 10 transcription factors we could explain early and in ten percent of the efforts can you read it observing whether we're starting the transcriptome on different condition so we studied around 300 conditions for every sport in the self-aware setting changes in gene expression as well we were relating is tainted with artificial factors or interpersonal something of this cool let me explain what this there are other elements underneath when we were starting also the structure of the chromosome and we realized that the super coding of the DNA in some vision is not important but then what will emulate these changes in the supercoiling also how it's fading or we simulated so there are several factors independently so the complexity is very hot so the idea of case will be we could study
properly the connection between the different pathways and the different and it was to really understand totally new system so this that's a cool we have and we doing that by using mycoplasma which is simple we could rise the level of knowledge but at least we could establish like the bases 2 2 later develop these models and simulations greatly because when people who've mathematical models with these negative networks then when you describe interaction strength and regulation or compression interaction between su dinero can use very different type of models you can use repressive later models marks action war base model and for any choice you do you have a completely different attitude and for the same network for the same graph if you do a choice or frequency later type of interaction likely a polygamist I / the output is completely different so do you have this type of experiment when you do your type of your simulation of you when you compare your simulations with reality at the end you have to do what you said compare with reality you have to compare with experimental data and see which is the one that is fitting matter to the results of the modeling that were doing so the lingo that you can do the simulations using different kinds of modeling but at the end the one that you consider that is a proper one is the man that is fitting matter with your spirit understand Patrick lyrically reproducing the physiology of the system some kind of ontological problem so at one side you have naughty work and you have the experiments we are you over your ideas to take your piece of reality plasma partitions to do something that year this thing has some kind of kind of interpretation so you you must to repeat experiments to see everything is def like the model or not so wide work of mathematician might work of model it is dis approach so I'd be anything that it's extracting new information from them alignment so that feather you need to collaborate but it's easier to collaborate something that you have an evident that's something that you have to start for blackpool I mean when you are Sperry Mentalist and you want to test hypotheses you can't have 100 people coughing focuses you have a way to discriminate them and I started which element which other priorities it facilitates hello from work so I think that at the end is it's good that you have this in that place between mathematics are not experimental questions will probably not only to you but for about models all these network best models always database models how robust way are two hidden information so we're based but we are no way below budget two years later viewing new people have new methods we will add some new informations how robust are our two day models to this unknown still unknown information how between potentially change results of modeling it will change exactly but how did somebody measure it it I don't know we do measure and I think this there'll always be more information that you can incorporate but if you if you are trying to predict a certain phenomenon you can look at how close you get to predicting actual observations and duniya experiments just to see what the error is and within the scheme of what you know if you get close to the observations I think I've always doing or they may not be completely Magnussen know what I what I mean for instance we have several functional models look for instance DNA pets outside yes we know some connections between cell cycle and DNA repair mechanisms and we are making some predictions for drug discoveries for instance etc two years later will we will find some new mechanisms which are connected probably we can find some Union and isn't some use or interactions which are connected with two models how attentional visit because I know but which is a well people of measured robustness in some statistical models by weight as accept some data yet and 20 and when tested the result the same probably we should add some attentional unknown informations people will share and some potentially possible informations about no not existing interactions not measured in corrections to test our our models robot quite robust put some new information about interactions between these functional models dramatically change results of our modeling well I think that I would work here is that the models at that is dependent so you have always their information from the components of the morning and also the reaction so you can always add a new reaction always as you know him and when you know the function of how they acting or the interplay between different element you can see move you can include these databases and then see which is the impact in the model I believe that the rebel depend who has to test the robustness of the modern I'll see which is the impact of these modifications on prolly you will end up doing new experiments to formality man we entering the topic of a standardization or so that I think that is final day oh they also they focusing on the ideas of lizards know do we have any scum nursing modeling and when you are in working
with different kinds of modeling are we using all the same languages are we using all the same understanding way to put little modifications in these waters so we are trying to find a way to standardize these and to have all the database external from the model so that you can only change some parameters or add some features and then this work will simulate or reproduce these changes on hold anything we go for final question or three getting closer macro end of the session the concept of the experiment in biology I have a lot of effort and a lot of work in drosophila with analyzing experimental data and the group in New York I need school they have done to following they they do the same experiment a bit annoyed and the output is is completely different it's called phenotypic variety and you have analyzed is bad that you know very well the genetic network it's only simply network with 12 no 12 jeans or not that you want to call them so we have the protein and RNA and all type of intellectual to everyone with very small network and what we have seen is that for each each each experiment you do everything in the same thing and the output is different so when you have 1x pairing method to establish well arrow in your network you have a problem in physics in general we say that when you prepare an experiment and the initial conditions are exactly there isn't a petrides we have the same out of here you have phenotypic reliability we have other questions then you begin to make model service and what happened is the forum in general you say that if you have a system with some fixed number of parameters if you change the parameters the output will be different so what you have found is exactly the following you have in the space of parameters of these networks you change there is a lot of you can change parameters and output is the same remains unchanged and the predictor really significantly very important to me so so I have this problem when you do an experiment how are you you make a specific very exact relationship between the input and the output so when you have because you don't know in fact very well the system when you have this engineering approach that you have put black box in your slides the output this is behind of this itself the engineered sinks and the physicist thinks that if I change into I get something you are not put at ease different part she's not different so i soooo why this parameter but in balance is not like that and the experiments as far as I know the only group that keep on repeating this experiment is this high needs for drosophila because everything is very very well known for each experiment for example for one protein decoy you have about 1000 experiments of distribution of the code and is also know is different so when you do an experiment you hit each other experiment or not we are always lean replicate analytically anything we can replicate him in order to have reproducible results I agree that sometimes mojadito body avidity but in the case of 50 videos were reproducible I think that it's all chilling with a complexity of the system so no winners of fear a local at excel and you have a pitch anything zabala where you have a lot of modification professional multiplications that are not linked to the genome or two they touch the condition that way when Marcus in reality seek is important cause you said that is about when you say vinyl you say two words I am always afraid is worth of optimization for me I travel and the world of you to have a standart we have some kind of thing like that because nothing is I suppose you want to make travel good travel from Miletus I pedestal and you can optimize from the soil and you can optimize on time those optimizations are completely different in biology you have ten thousand genes I don't know for example your k7 engines what the animal dependent of the environment the optimizes are many are many genes Felicity optimizes for three or five objectives so you have a pareto front you don't have a unique solution the solution is enormous our enormous space of solutions so when you try to make a kind of you say lower optimization optimization so you have only one parameter optimizations are well he's only well defined for one parameter if you have to keep our track but if you have to mean instructions we can lock the manager meaning these are songs also for the at a very lively discussion on limits and challenges of models we add up with limits and challenges in biology to repeat experiments I will that on this may be a bit later we about it on Monday the question standardization of experiments by Paul Freeman is saying that reduces through the same direction i think i would like to close the session and thank the audience for the questions and also for our speakers