In Silico Cell-Type Deconvolution Methods in Cancer Immunotherapy

2020 ◽  
pp. 213-222
Author(s):  
Gregor Sturm ◽  
Francesca Finotello ◽  
Markus List
Keyword(s):  
Cancer Immunotherapy ◽  
In Silico ◽  
Cell Type

scholarly journals In silico dissection of cell-type-associated patterns of gene expression in prostate cancer

2004 ◽  
Vol 101 (2) ◽  
pp. 615-620 ◽  
Author(s):  
R. O. Stuart ◽  
W. Wachsman ◽  
C. C. Berry ◽  
J. Wang-Rodriguez ◽  
L. Wasserman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
In Silico ◽  
Cell Type

scholarly journals Gene expression in isolated cowpea (Vigna unguiculata L. Walp) cells from meiosis to seed initiation

2020 ◽  
Author(s):  
Nial Gursanscky ◽  
Danielle Mazurkiewicz ◽  
Martina Juranić ◽  
Susan D. Johnson ◽  
Gloria León ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Gene Silencing ◽  
Histone Modification ◽  
In Silico ◽  
Female Gametophyte ◽  
Cell Type ◽  
Cell Specification ◽  
Seed Formation ◽  
Male And Female

AbstractMolecular knowledge of pathways regulating seed formation in legumes, remains scarce. Thirteen isolated cell-type transcriptomes were developed, spanning temporal events of male and female gametogenesis and seed initiation, to examine pathways involved in cowpea seed formation. In situ hybridization confirmed localization of in silico identified cell-specific genes, verifying transcriptome utility. Cowpea and Arabidopsis reproductive cells showed some conservation in regulators enabling cell-type expression as some cowpea cell-specific genes promoters and their Arabidopsis homologs directed expression to identical reproductive cell-types in transgenic plants. In silico analyses revealed gene expression similarities and differences with genes in pathways regulating reproductive events in other plants. Meiosis-related genes were expressed at mitotic stages of gametogenesis and during sporophytic development in cowpea. Plant hormone pathways showing preferential expression at particular reproductive stages were identified. Expression of epigenetic pathways, resembling those found in Arabidopsis, including microRNA mediated gene silencing, RNA directed DNA methylation and histone modification were associated with particular stages of male and female gametophyte development, suggesting roles in gametogenic cell specification and elaboration. Analyses of cell-cycle related gene expression in mature cowpea female gametophytes, indicated that the egg and central cell were arrested at the G1/S and G2/M cell cycle phases, respectively, prior to fertilization. Pre-fertilization female gametophyte arrest was characterized by barely detectable auxin biosynthesis gene expression levels, and elevated expression of genes involved in RNA-mediated gene silencing and histone modification. These transcriptomes provide a useful resource for additional interrogation to support functional analyses for development of higher yielding cowpea and syntenic legume crops.One sentence summaryAnalyses of laser capture derived cell-type transcriptomes spanning meiosis to seed initiation revealed gene expression profiles during cell specification and reproductive development in cowpea.

scholarly journals CDSeqR: fast complete deconvolution for gene expression data from bulk tissues

2021 ◽  
Author(s):  
Kai Kang ◽  
Caizhi David Huang ◽  
Yuanyuan Li ◽  
David M. Umbach ◽  
Leping Li
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
In Silico ◽  
Cell Types ◽  
R Package ◽  
Biological Tissues ◽  
Specific Cell ◽  
Rna Seq ◽  
Cell Type ◽  
Cell Type Specific

AbstractBackgroundBiological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and with a new function to aid interpretation of deconvolution outcomes. The R package would be of interest for the broader R community.ResultWe developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating CDSeq-estimated cell types using publicly available single-cell RNA sequencing (scRNA-seq) data (single-cell data from 20 major organs are included in the R package). This function allows users to readily interpret and visualize the CDSeq-estimated cell types. We carried out additional validations of the CDSeqR software with in silico and in vitro mixtures and with real experimental data including RNA-seq data from the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) project.ConclusionsThe existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell-cell interactions in the tissue microenvironment. However, bulk level analyses neglect tissue heterogeneity and hinder investigation in a cell-type-specific fashion. The CDSeqR package can be viewed as providing in silico single-cell dissection of bulk measurements. It enables researchers to gain cell-type-specific information from bulk RNA-seq data.

Bevacizumab Antibody Affinity Maturation to Improve Ovarian Cancer Immunotherapy: In Silico Approach

2018 ◽  
Vol 25 (4) ◽  
pp. 1417-1430
Author(s):  
Shirin Eyvazi ◽  
Zahra Payandeh ◽  
Saeed Khalili ◽  
Fatemeh Sefid ◽  
Elaheh Ouladsahebmadarek
Keyword(s):  
Ovarian Cancer ◽  
Cancer Immunotherapy ◽  
In Silico ◽  
Affinity Maturation ◽  
Antibody Affinity

scholarly journals Use of an in silico knowledge discovery approach to determine mechanistic studies of silver nanoparticles-induced toxicity from in vitro to in vivo

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Bin-Hsu Mao ◽  
Yi-Kai Luo ◽  
Bour-Jr Wang ◽  
Chun-Wan Chen ◽  
Fong-Yu Cheng ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Knowledge Discovery ◽  
Exposure Time ◽  
In Silico ◽  
Surface Coating ◽  
Exposure Dose ◽  
Morphological Observation ◽  
Cell Type

Abstract Background Silver nanoparticles (AgNPs) are considered a double-edged sword that demonstrates beneficial and harmful effects depending on their dimensions and surface coating types. However, mechanistic understanding of the size- and coating-dependent effects of AgNPs in vitro and in vivo remains elusive. We adopted an in silico decision tree-based knowledge-discovery-in-databases process to prioritize the factors affecting the toxic potential of AgNPs, which included exposure dose, cell type and AgNP type (i.e., size and surface coating), and exposure time. This approach also contributed to effective knowledge integration between cell-based phenomenological observations and in vitro/in vivo mechanistic explorations. Results The consolidated cell viability assessment results were used to create a tree model for generalizing cytotoxic behavior of the four AgNP types: SCS, LCS, SAS, and LAS. The model ranked the toxicity-related parameters in the following order of importance: exposure dose > cell type > particle size > exposure time ≥ surface coating. Mechanistically, larger AgNPs appeared to provoke greater levels of autophagy in vitro, which occurred during the earlier phase of both subcytotoxic and cytotoxic exposures. Furthermore, apoptosis rather than necrosis majorly accounted for compromised cell survival over the above dosage range. Intriguingly, exposure to non-cytotoxic doses of AgNPs induced G2/M cell cycle arrest and senescence instead. At the organismal level, SCS following a single intraperitoneal injection was found more toxic to BALB/c mice as compared to SAS. Both particles could be deposited in various target organs (e.g., spleen, liver, and kidneys). Morphological observation, along with serum biochemical and histological analyses, indicated that AgNPs could produce pancreatic toxicity, apart from leading to hepatic inflammation. Conclusions Our integrated in vitro, in silico, and in vivo study revealed that AgNPs exerted toxicity in dose-, cell/organ type- and particle type-dependent manners. More importantly, a single injection of lethal-dose AgNPs (i.e., SCS and SAS) could incur severe damage to pancreas and raise blood glucose levels at the early phase of exposure.

scholarly journals In silico cancer immunotherapy trials uncover the consequences of therapy-specific response patterns for clinical trial design and outcome

2021 ◽  
Author(s):  
Jeroen H.A. Creemers ◽  
Kit C.B. Roes ◽  
Niven Mehra ◽  
Carl G. Figdor ◽  
I. Jolanda M. de Vries ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Tumor Microenvironment ◽  
Cancer Immunotherapy ◽  
In Silico ◽  
Trial Design ◽  
Clinical Trial Design ◽  
Specific Response ◽  
Response Patterns ◽  
Biological Interactions

ABSTRACTBackgroundLate-stage cancer immunotherapy trials strive to demonstrate the clinical efficacy of novel immunotherapies, which is leading to exceptional responses and long-term survival in subsets of patients. To establish the clinical efficacy of an immunotherapy, it is critical to adjust the trial’s design to the expected immunotherapy-specific response patterns.MethodsIn silico cancer immunotherapy trials are virtual clinical trials that simulate the kinetics and outcome of immunotherapy depending on the type and treatment schedule. We used an ordinary differential equation model to simulate (1) cellular interactions within the tumor microenvironment, (2) translates these into disease courses in patients, and (3) assemble populations of virtual patients to simulate in silico late-stage immunotherapy, chemotherapy, or combination trials. We predict trial outcomes and investigate how therapy-specific response patterns affect the probability of their success.ResultsIn silico cancer immunotherapy trials reveal that immunotherapy-derived survival kinetics – such as delayed curve separation and plateauing curve of the treatment arm – arise naturally due to biological interactions in the tumor microenvironment. In silico clinical trials are capable of translating these biological interactions into survival kinetics. Considering four aspects of clinical trial design – sample size calculations, endpoint and randomization rate selection, and interim analysis planning – we illustrate that failing to consider such distinctive response patterns can significantly reduce the power of novel immunotherapy trials.ConclusionIn silico trials have three significant implications for immuno-oncology. First, they provide an economical approach to verify the robustness of biological assumptions underlying an immunotherapy trial and help to scrutinize its design. Second, the biological basis of these trials facilitates and encourages communication between biomedical researchers, doctors, and trialists. Third, its application as an educational tool can illustrate design principles to scientists in training, contributing to improved designs and higher success rates of future immunotherapy trials.

Ultrastructural Correlations between Clonal Human Tumor Colonies and in Vivo Neoplasms

1982 ◽  
Vol 40 ◽  
pp. 210-211
Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman
Keyword(s):  
Cultured Cells ◽  
Human Tumor ◽  
Cell Type ◽  
Tumor Mass ◽  
Initial Cell ◽  
Cloning Assay ◽  
Human Tumor Cloning ◽  
The Relationship

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.

Some Observations on Changes in Denervated Taste Buds of Circumvallate Papillae of Rabbits

1969 ◽  
Vol 27 ◽  
pp. 308-309
Author(s):  
Sunao Fujimoto ◽  
Raymond G. Murray ◽  
Assia Murray
Keyword(s):  
Taste Buds ◽  
Taste Bud ◽  
Cell Type ◽  
Dark Cells ◽  
Type Iii ◽  
Circumvallate Papillae ◽  
Taste Bud Cells ◽  
Light Cells

Taste bud cells in circumvallate papillae of rabbit have been classified into three groups: dark cells; light cells; and type III cells. Unilateral section of the 9th nerve distal to the petrosal ganglion was performed in 18 animals, and changes of each cell type in the denervated buds were observed from 6 hours to 10 days after the operation.Degeneration of nerves is evident at 12 hours (Fig. 1) and by 2 days, nerves are completely lacking in the buds. Invasion by leucocytes into the buds is remarkable from 6 to 12 hours but then decreases. Their extrusion through the pore is seen. Shrinkage and disturbance in arrangement of cells in the buds can be seen at 2 days. Degenerated buds consisting of a few irregular cells and remnants of degenerated cells are present at 4 days, but buds apparently normal except for the loss of nerve elements are still present at 6 days.

Dendritic cells of the human epidermis: immuno-electron microscopic studies of la antigen reactivity

1978 ◽  
Vol 36 (2) ◽  
pp. 644-645
Author(s):  
G. Rowden ◽  
M. G. Lewis ◽  
T. M. Phillips
Keyword(s):  
Dendritic Cells ◽  
Langerhans Cells ◽  
Cell Types ◽  
Cell Type ◽  
Electron Microscopic ◽  
La Antigen ◽  
Microscopic Studies ◽  
A Cell ◽  
C3 Receptors ◽  
Antigen Reactivity

Langerhans cells of mammalian stratified squamous epithelial have proven to be an enigma since their discovery in 1868. These dendritic suprabasal cells have been considered as related to melanocytes either as effete cells, or as post divisional products. Although grafting experiments seemed to demonstrate the independence of the cell types, much confusion still exists. The presence in the epidermis of a cell type with morphological features seemingly shared by melanocytes and Langerhans cells has been especially troublesome. This so called "indeterminate", or " -dendritic cell" lacks both Langerhans cells granules and melanosomes, yet it is clearly not a keratinocyte. Suggestions have been made that it is related to either Langerhans cells or melanocyte. Recent studies have unequivocally demonstrated that Langerhans cells are independent cells with immune function. They display Fc and C3 receptors on their surface as well as la (immune region associated) antigens.

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