37 research outputs found
Forum on immune digital twins: a meeting report
Medical digital twins are computational models of human biology relevant to a
given medical condition, which can be tailored to an individual patient,
thereby predicting the course of disease and individualized treatments, an
important goal of personalized medicine. The immune system, which has a central
role in many diseases, is highly heterogeneous between individuals, and thus
poses a major challenge for this technology. If medical digital twins are to
faithfully capture the characteristics of a patient's immune system, we need to
answer many questions, such as: What do we need to know about the immune system
to build mathematical models that reflect features of an individual? What data
do we need to collect across the different scales of immune system action? What
are the right modeling paradigms to properly capture immune system complexity?
In February 2023, an international group of experts convened in Lake Nona, FL
for two days to discuss these and other questions related to digital twins of
the immune system. The group consisted of clinicians, immunologists,
biologists, and mathematical modelers, representative of the interdisciplinary
nature of medical digital twin development. A video recording of the entire
event is available. This paper presents a synopsis of the discussions, brief
descriptions of ongoing digital twin projects at different stages of progress.
It also proposes a 5-year action plan for further developing this technology.
The main recommendations are to identify and pursue a small number of promising
use cases, to develop stimulation-specific assays of immune function in a
clinical setting, and to develop a database of existing computational immune
models, as well as advanced modeling technology and infrastructure
iTools: A Framework for Classification, Categorization and Integration of Computational Biology Resources
The advancement of the computational biology field hinges on progress in three fundamental directions – the development of new computational algorithms, the availability of informatics resource management infrastructures and the capability of tools to interoperate and synergize. There is an explosion in algorithms and tools for computational biology, which makes it difficult for biologists to find, compare and integrate such resources. We describe a new infrastructure, iTools, for managing the query, traversal and comparison of diverse computational biology resources. Specifically, iTools stores information about three types of resources–data, software tools and web-services. The iTools design, implementation and resource meta - data content reflect the broad research, computational, applied and scientific expertise available at the seven National Centers for Biomedical Computing. iTools provides a system for classification, categorization and integration of different computational biology resources across space-and-time scales, biomedical problems, computational infrastructures and mathematical foundations. A large number of resources are already iTools-accessible to the community and this infrastructure is rapidly growing. iTools includes human and machine interfaces to its resource meta-data repository. Investigators or computer programs may utilize these interfaces to search, compare, expand, revise and mine meta-data descriptions of existent computational biology resources. We propose two ways to browse and display the iTools dynamic collection of resources. The first one is based on an ontology of computational biology resources, and the second one is derived from hyperbolic projections of manifolds or complex structures onto planar discs. iTools is an open source project both in terms of the source code development as well as its meta-data content. iTools employs a decentralized, portable, scalable and lightweight framework for long-term resource management. We demonstrate several applications of iTools as a framework for integrated bioinformatics. iTools and the complete details about its specifications, usage and interfaces are available at the iTools web page http://iTools.ccb.ucla.edu
Global Search for Minimum Energy (H2O)n Clusters, n = 3−5
The Gaussian-3 (G3) model chemistry method has been used to calculate the relative ΔG° values for all possible conformers of neutral clusters of water, (H2O)n, where n = 3−5. A complete 12-fold conformational search around each hydrogen bond produced 144, 1728, and 20 736 initial starting structures of the water trimer, tetramer, and pentamer. These structures were optimized with PM3, followed by HF/6-31G* optimization, and then with the G3 model chemistry. Only two trimers are present on the G3 potential energy hypersurface. We identified 5 tetramers and 10 pentamers on the potential energy and free-energy hypersurfaces at 298 K. None of these 17 structures were linear; all linear starting models folded into cyclic or three-dimensional structures. The cyclic pentamer is the most stable isomer at 298 K. On the basis of this and previous studies, we expect the cyclic tetramers and pentamers to be the most significant cyclic water clusters in the atmosphere
Pople\u27s Gaussian-3 model chemistry applied to an investigation of (H2O)8 water clusters
The Gaussian-3 method developed by Pople and coworkers has been used to calculate the free energy of neutral octamer clusters of water, (H2O)8. The most energetically stable structures are in excellent agreement with those determined from experiment and those predicted from previous high-level calculations. Cubic structures are favored over noncubic structures over all temperature ranges studied. The D2d cubic structure is the lowest free energy structure and dominates the potential energy and free energy hypersurfaces from 0 K to 298 K
Increased expression of interferon-inducible genes in macaque lung tissues during simian immunodeficiency virus infection
Pulmonary infections and dysfunction are frequent outcomes during the development of immunodeficiency associated with human immunodeficiency virus type 1 (HIV-1) infection, and obtaining a better understanding of the immunologic changes that occur in lungs following HIV-1 infection will provide a foundation for the development of further intervention strategies. We sought here to identify changes
in the pulmonary immune environment that arise during simian immunodeficiency virus (SIV) infection of rhesus macaques, which serves
as an excellent model system for HIV-1 infection and disease. To examine the gene expression profiles of macaque lung tissues following
infection with the pathogenic SIV/DeltaB670 isolate, we performed cDNA microarray hybridizations with lung total RNAs using two commercially available cDNA arrays and a custom-fabricated, immunologically focused macaque cDNA microarray. In situ hybridization and
real-time RT-PCR were performed to provide additional analyses of gene expression. Among the genes exhibiting the highest level of induction in lung tissues were the IFN-gamma-inducible chemokines, CXCL10/IP-10 and CXCL9/Mig. In situ hybridization and real-time RT-PCR
strongly supported these findings. Correlation analyses revealed that the levels of expression of IFN-gamma, CXCL9/Mig, and CXCL10/IP-10
mRNAs were all strongly positively correlated, and that CXCL10/IP-10 mRNA and Pneumocystis carinii rRNA were positively correlated.
Taken together, these findings demonstrate that inflammatory chemokines are among the most differentially expressed mRNAs in macaque lung tissues during systemic SIV infection of rhesus macaques, and provide insight into the complicated events occurring in the lung tissues during HIV-1 infection in humans.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83357/1/Schaefer-et-al.2006.pd
Virologic and Immunologic Events in Hilar Lymph Nodes During Simian Immunodeficiency Virus Infection - Development of Polarized Inflammation
Lymphoid tissues are sites of soluble and cell-associated
antigen sampling of peripheral tissues, and they are key compart-
ments for the generation of cellular and humoral immune responses.
Hilar lymph nodes (HiLNs), which drain the lungs, were examined to
understand the effects of simian immunodeficiency virus (SIV) infec-
tion on this compartment of the immune system. Histologic and
messenger RNA (mRNA) expression profiling approaches were used
to determine the numbers, types, and distributions of SIV viral RNA+
cells and to identify differentially expressed genes in HiLNs during
SIV infection. SIV RNA+ cells were found to be primarily CD682 and
localized to paracortical and medullary regions early in infection,
whereas they resided mainly in paracortex during AIDS. As SIV
infection progressed, CXCL9, CXCL10, interferon-g, and Toll-like
receptor 3 levels all increased. In contrast, CCL19 increased early in
infection but decreased during AIDS, whereas CCL21 decreased
progressively throughout infection. Finally, local levels of cellular
activation were increased throughout infection. Taken together, these
findings indicate that SIV infection leads to an inflammatory envi-
ronment in lung-draining lymph nodes that is characterized by type 1
cytokines and chemokines and likely has an impact on the nature and
strength of immune responses to pulmonary pathogens.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83336/1/Fallert_et_al.2008.Virologic_and_Immunologic_Events_in_Hilar_Lymph.2.pd