C-ImmSim
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C-ImmSim started, in 1995, as the C-language "version" of IMMSIM, the IMMune system SIMulator, a program written back in 1991 in APL-2 (APL2 is a Registered Trademark of IBM Corp.) by the astrophysicist Phil E. Seiden together with the immunologist Franco Celada to implement the Celada-Seiden model. The porting was mainly conducted and further developed by Filippo Castiglione with the help of few other people.
The Celada-Seiden model is a logical description of the mechanisms making up the adaptive immune humoral and cellular response to a genetic antigen at the mesoscopic level.
The computational counterpart of the Celada-Seiden model is the IMMSIM code.
The Celada-Seiden model, as well as C-ImmSim, is best viewed as a collection of models in a single program. In fact, there are various components realising a particular function which can be turned on or off. At its current stage, C-ImmSim incorporates the principal "core facts" of today's immunological knowledge, e.g.
- the diversity of specific elements,
- MHC restriction,
- clonal selection by antigen affinity,
- thymic education of T cells, antigen processing and presentation (both the cytosolic and endocytic pathways are implemented,
- cell-cell cooperation,
- homeostasis of cells created by the bone marrow,
- hypermutation of antibodies,
- maturation of the cellular and humoral response and memory.
Besides, an antigen can represent a bacterium, a virus or an allergen or a tumour cell.
The high degree of complexity of the Celada-Seiden model makes it suitable to simulate different immunological phenomena, e.g., the hypermutation of antibodies, the germinal centre reaction (GCR), immunization, Thymus selection, viral infections, hypersensitivity, etc.
Since the first release of C-ImmSim, the code has been modified many times. The actual version now includes features that were not in the original Celada-Seiden model.
C-ImmSim has been recently customised to simulate the HIV-1 infection. Moreover, it can simulate the immunotherapy to generic solid tumours. These features are all present in the code and people can choose to turn them on and off at compiling time. However, the present user guide deals with the description of the standard immune system response and gives no indication on the features of HIV-1 and cancer.
The latest version of C-ImmSim allows for the simulation of SARS-CoV-2 infection .[1]
Contributors
The porting was possible thank to the aid of Seiden, especially during the initial validation phase. Massimo Bernaschi contributed to the development of C-ImmSim starting as the "beta" release. Most of the optimization of the memory usage and I/O has been possible thanks to Bernaschi in particular for what concerns the development of the parallel version. Other few people contributed to the further development of the code in the coming years.