EP1656629A2 - Verfahren zur modellierung und simulation eines biologischen systems und modell zur ausführung dieses verfahrens - Google Patents
Verfahren zur modellierung und simulation eines biologischen systems und modell zur ausführung dieses verfahrensInfo
- Publication number
- EP1656629A2 EP1656629A2 EP04786288A EP04786288A EP1656629A2 EP 1656629 A2 EP1656629 A2 EP 1656629A2 EP 04786288 A EP04786288 A EP 04786288A EP 04786288 A EP04786288 A EP 04786288A EP 1656629 A2 EP1656629 A2 EP 1656629A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- transformation
- biological functional
- biological
- functional entities
- functional entity
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000009466 transformation Effects 0.000 claims abstract description 54
- 230000002123 temporal effect Effects 0.000 claims abstract description 18
- 230000000877 morphologic effect Effects 0.000 claims abstract description 14
- 238000000844 transformation Methods 0.000 claims abstract description 14
- 230000000694 effects Effects 0.000 claims abstract description 7
- 125000004429 atom Chemical group 0.000 claims description 6
- 230000006870 function Effects 0.000 claims description 5
- 108090000623 proteins and genes Proteins 0.000 claims description 5
- 102000004169 proteins and genes Human genes 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 238000005842 biochemical reaction Methods 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 210000004027 cell Anatomy 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 230000008439 repair process Effects 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000002209 hydrophobic effect Effects 0.000 claims description 3
- 210000003463 organelle Anatomy 0.000 claims description 3
- 230000002085 persistent effect Effects 0.000 claims description 3
- 230000001323 posttranslational effect Effects 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 claims description 3
- 230000035800 maturation Effects 0.000 claims description 2
- 230000006820 DNA synthesis Effects 0.000 claims 1
- 239000000470 constituent Substances 0.000 abstract 2
- 238000004088 simulation Methods 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 238000005411 Van der Waals force Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000030609 dephosphorylation Effects 0.000 description 2
- 238000006209 dephosphorylation reaction Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000004422 calculation algorithm Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 238000013507 mapping Methods 0.000 description 1
- 230000006740 morphological transformation Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 108700026220 vif Genes Proteins 0.000 description 1
Classifications
-
- G—PHYSICS
- G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
- G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
- G16B5/00—ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
Definitions
- the present invention relates to methods of modeling and simulating biological systems. Such methods have already been described for example by ROUX-ROUQUIE et al. (RC Biologies 325 (2002) 419-430).
- the methods of modeling and simulation of known biological systems have the disadvantage of being carried out on a case-by-case basis, in a non-standardized manner, so that they are incompatible with one another and difficult to understand by biologists not versed in applied mathematics. , therefore difficult to validate and of random reliability.
- the present invention aims in particular to overcome these drawbacks.
- the invention proposes a method of modeling and simulating a biological system comprising at least tangible biological functional entities (that is to say constituted by matter), modeled by at least: one morphological occurrence, comprising at least one biochemical component identifying the persistent properties of the biological functional entity and at least one transformation representative of the way in which this component evolves according to the spatio-temporal context, a spatial occurrence, representative of at least one spatial characteristic of the biological functional entity and a temporal occurrence, representative of at least one temporal characteristic of the biological functional entity, process in which one simulates an evolution of said biological functional entities by recursively determining the effect of any changes affecting these occurrences, including transformations, on their functioning and their evolution (their activities).
- the modeling and simulation method according to the invention distinguishes: - on the one hand, the persistent characters (designated in the invention by "components") of the entities forming the biological system in question (name, category; for example : a cell, a nucleus, a protein, etc.), and on the other hand, the functional states of these components which are dependent on the active morphological occurrence of these entities and on the spatio-temporal context in which they exercise their activities . Thanks to these provisions, the modeling of the biological system to be simulated • is carried out in an explicit, standardizable, logical and easily accessible way to a biologist not specialized in mathematics or programming (the biologist can indeed easily check in particular the morphological and spatial characteristics. which are factual).
- the method according to the invention separates simulation, which can use various mathematical calculation methods, and modeling: thus, it is possible to apply several simulation methods to the same model of biological system, that is to say during successive simulations, or simultaneously by applying several types of simulation to different parts of the biological system.
- the temporal occurrence is chosen from an age of the biological functional entity and a period during which the functional entity is active; said biological component is chosen from an organism, a tissue, a cell, an organelle and a molecule; said transformation is chosen from a cellular transformation and a molecular transformation; said transformation is a molecular transformation, chosen from: a covalent molecular transformation, itself chosen from: a covalent transformation of proteins corresponding to a co-translational or post-translational transformation (such as phosphorylation or dephosphorylation), a transformation covalent RNA corresponding to synthesis or maturation of RNA, and covalent transformation of DNA corresponding to synthesis, damage or repair of DNA,.
- the temporal occurrence is chosen from an age of the biological functional entity and a period during which the functional entity is active
- said biological component is chosen from an organism, a tissue, a cell, an organelle and a molecule
- said transformation is chosen from a cellular transformation and a molecular transformation
- said transformation is a mo
- a non-covalent transformation itself chosen from: a hydrophobic transformation, a transformation due to the use of Van der Waals forces, a transformation due to the use of electrostatic forces, a transformation due to an attraction between an electronegative atom of one molecule and a hydrogen atom of another molecule, and a steric transformation due to an attraction between neighboring atoms; some of said biological functional entities are included in at least at least one superior biological functional entity; at least some of said biological functional entities include lower biological functional entities; certain functional entities constitute the environment of at least certain other functional entities with which they interact; the biological system also includes intangible biological functional entities, modeled by temporal occurrences and, where appropriate, spatial and morphological; said biological functional entities intangibles include biochemical reactions.
- the invention also relates to a model of biological system intended in particular (but not exclusively) for the implementation of the method as defined above, this model comprising at least tangible biological functional entities, modeled by at minus: a morphological occurrence, comprising at least one biochemical component identifying the biological functional entity and at least one transformation representative of the way in which this component evolves as a function of the space-time context, a spatial occurrence, representative of at least one characteristic spatial of said biological functional entity; and a temporal occurrence, representative of at least one temporal characteristic of the biological functional entity.
- a morphological occurrence comprising at least one biochemical component identifying the biological functional entity and at least one transformation representative of the way in which this component evolves as a function of the space-time context, a spatial occurrence, representative of at least one characteristic spatial of said biological functional entity; and a temporal occurrence, representative of at least one temporal characteristic of the biological functional entity.
- the invention proposes a meta-model which is particularly suitable for modeling biological systems, in particular with a view to simulating the evolution of these systems.
- the biological system is modeled as a set of biological functional entities, tangible or intangible.
- Each of these biological functional entities when it is a tangible biological functional entity, is modeled by at least: a morphological occurrence, comprising at least one biochemical component identifying the biological functional entity and at least one transformation representative of how this component evolves into function of the spatio-temporal context, in particular following interactions with other biological functional entities, a temporal occurrence, representative of at least one temporal characteristic of the biological functional entity (in particular the age of this entity and / or a period activity of this entity), and a spatial occurrence, representative of at least one spatial characteristic of the biological functional entity (corresponding for example to the position of the biological functional entity with respect to its external environment).
- Each tangible biological functional entity may optionally be included in a higher biological • functional entity, and / or include itself biological less functional entities.
- at least certain functional entities can constitute the environment of at least certain other functional entities with which they interact.
- the biochemical components mentioned above may include, for example: a living organism, a biological tissue, a cell, for example an epithelial cell or a lymphocyte cell, an organelle, for example a nucleus or a ribose, and a molecule, for example a RNA molecule, a DNA element (for example a gene, a regulatory element or a promoter), or a protein.
- the aforementioned transformations may include, for example, cellular transformations and molecular transformations. The molecular transformations in question.
- covalent protein transformations in particular post-translational transformations such as phosphorylation or dephosphorylation, and co-translational transformations
- covalent transformations of RNA in particular syntheses and splices
- covalent transformations of DNA in particular synthesis, damage and repair by basic excision, by recombination, by excision of nucleotides, by photoreactivation and repair of pairings]
- hydrophobic non-covalent molecular transformations or due to the use of Van der Waals forces, or due to the implementation of electrostatic forces, or due to an attraction between an electronegative atom of a molecule and a hydrogen atom of another molecule or steric transformations due to an attraction between neighboring atoms (in particular phosphoisomerization)
- at least some of the biological functional entities modeling the biological system can be d intangible biological functional entities, including biochemical reactions.
- intangible biological functional entities may not have morphological occurrences, in which case they will only include temporal and if necessary spatial occurrences.
- the aforementioned modeling of the biological system can be carried out in particular using the UML TM object language and the functional units modeled as active objects of UML TM, which facilitates translation.
- mapping to formal languages facilitating analysis and simulation, for example Pi computation.
- the state of each biological functional entity is defined at all times by the values of these morphological, temporal and spatial occurrences, and the behavior of the biological system over time is represented by the trajectory of the states of each biological functional entity in the repository (shape, time, space) .
- the behavior of the biological functional entities is simulated over time, recursively, by determining step by step whether at least some of the morphological transformations of said biological functional entities occur as a function of the spatio-temporal context, as interactions between biological functional entities progress.
- performing an action changes the value of the shape instance and changes the state of the functional entity which then performs a transition, for example by going from the inactive state to the 'active state; the realization of this new state constitutes an event which can trigger another action, such as for example, the transfer of the functional entity from one cellular compartment to another by modifying the value of the spatial occurrence
- the meta-model according to the invention can be used for example to model and simulate: biochemical reactions, in which case the morphological occurrences of the biological functional entities (for example enzymes) include the biochemical components which are the subject of these reactions.
- these functional entities “population” may include for example, concentrations of these components, reactions to simulate then being modeled in a "protocol” file or by the morphological characteristics of a higher biological functional entity, and the simulation being made for example by solving differential equations as in the software known as "E-cell” or by a stochastic algorithm as in the software known as name “Stochsim”; any biological process, using for example the simulation means of the known software "Genomic Object Net".
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Physiology (AREA)
- Bioinformatics & Computational Biology (AREA)
- Biotechnology (AREA)
- Evolutionary Biology (AREA)
- General Health & Medical Sciences (AREA)
- Medical Informatics (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Theoretical Computer Science (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Measuring And Recording Apparatus For Diagnosis (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0309983A FR2859031A1 (fr) | 2003-08-18 | 2003-08-18 | Procede de modelisation et de simulation d'un systeme biologique et modele pour la mise en oeuvre de ce procede |
| PCT/FR2004/002115 WO2005020119A2 (fr) | 2003-08-18 | 2004-08-10 | Procede de modelisation et de simulation d’un systeme biologique et modele pour la mise en oeuvre de ce procede |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1656629A2 true EP1656629A2 (de) | 2006-05-17 |
Family
ID=34112800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP04786288A Withdrawn EP1656629A2 (de) | 2003-08-18 | 2004-08-10 | Verfahren zur modellierung und simulation eines biologischen systems und modell zur ausführung dieses verfahrens |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20060292702A1 (de) |
| EP (1) | EP1656629A2 (de) |
| CA (1) | CA2536250A1 (de) |
| FR (1) | FR2859031A1 (de) |
| WO (1) | WO2005020119A2 (de) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20160281094A1 (en) * | 2015-03-28 | 2016-09-29 | John C. Weast | Technologies for manufacturing an engineered bio-system |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5930154A (en) * | 1995-01-17 | 1999-07-27 | Intertech Ventures, Ltd. | Computer-based system and methods for information storage, modeling and simulation of complex systems organized in discrete compartments in time and space |
-
2003
- 2003-08-18 FR FR0309983A patent/FR2859031A1/fr active Pending
-
2004
- 2004-08-10 EP EP04786288A patent/EP1656629A2/de not_active Withdrawn
- 2004-08-10 WO PCT/FR2004/002115 patent/WO2005020119A2/fr not_active Ceased
- 2004-08-10 US US10/568,718 patent/US20060292702A1/en not_active Abandoned
- 2004-08-10 CA CA002536250A patent/CA2536250A1/fr not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005020119A2 * |
Also Published As
| Publication number | Publication date |
|---|---|
| US20060292702A1 (en) | 2006-12-28 |
| WO2005020119A3 (fr) | 2005-11-03 |
| CA2536250A1 (fr) | 2005-03-03 |
| WO2005020119A2 (fr) | 2005-03-03 |
| FR2859031A1 (fr) | 2005-02-25 |
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| DAX | Request for extension of the european patent (deleted) | ||
| 17Q | First examination report despatched |
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| STAA | Information on the status of an ep patent application or granted ep patent |
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