scholarly journals Pharmacogenomic Biomarkers

2002 ◽  
Vol 18 (2) ◽  
pp. 63-71 ◽  
Author(s):  
Sandra C. Kirkwood ◽  
Richard D. Hockett
Keyword(s):  
Complex Disease ◽  
Retrospective Studies ◽  
Molecular Classification ◽  
Great Promise ◽  
Widespread Application ◽  
Response Efficacy ◽  
Genetic Biomarkers ◽  
Disease States ◽  
Genetic Biomarker

Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

scholarly journals Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment

2005 ◽  
Vol 201 (3) ◽  
pp. 373-383 ◽  
Author(s):  
Isabelle J. Fugier-Vivier ◽  
Francine Rezzoug ◽  
Yiming Huang ◽  
Amanda J. Graul-Layman ◽  
Carrie L. Schanie ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Great Promise ◽  
Widespread Application ◽  
Hematopoietic Stem ◽  
Disease States ◽  
Skin Allografts ◽  
Cell Engraftment ◽  
Tnf Α ◽  
Functional Features ◽  
Donor Specific Tolerance

Bone marrow transplantation offers great promise for treating a number of disease states. However, the widespread application of this approach is dependent upon the development of less toxic methods to establish chimerism and avoid graft-versus-host disease (GVHD). CD8+/TCR− facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. In the present studies, we have identified the main subpopulation of FCs as plasmacytoid precursor dendritic cells (p-preDCs). FCs and p-preDCs share many phenotypic, morphological, and functional features: both produce IFN-α and TNF-α, both are activated by toll-like receptor (TLR)-9 ligand (CpG ODN) stimulation, and both expand and mature after Flt3 ligand (FL) treatment. FL-mobilized FCs, most of which express a preDC phenotype, significantly enhance engraftment of HSCs and induce donor-specific tolerance to skin allografts. However, p-preDCs alone or p-preDCs from the FC population facilitate HSC engraftment less efficiently than total FCs. Moreover, FCs depleted of preDCs completely fail to facilitate HSC engraftment. These results are the first to define a direct functional role for p-preDCs in HSC engraftment, and also suggest that p-preDCs need to be in a certain state of maturation/activation to be fully functional.

Molecular classification of pituitary adenomas

2015 ◽  
Author(s):  
Antonio Pico ◽  
Laura Sanchez-Tejada ◽  
Ruth Sanchez-Ortiga ◽  
Rosa Camara ◽  
Cristina Lamas ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Molecular Classification

scholarly journals Normal tissue content impact on the GBM molecular classification

2020 ◽  
Author(s):  
Rodrigo Madurga ◽  
Noemí García-Romero ◽  
Beatriz Jiménez ◽  
Ana Collazo ◽  
Francisco Pérez-Rodríguez ◽  
...  
Keyword(s):  
Normal Tissue ◽  
In Silico Analysis ◽  
Molecular Classification ◽  
Gene Signature ◽  
Normal Brain ◽  
Normal Cells ◽  
Final Model ◽  
Tumor Subtypes ◽  
Tissue Content

Abstract Molecular classification of glioblastoma has enabled a deeper understanding of the disease. The four-subtype model (including Proneural, Classical, Mesenchymal and Neural) has been replaced by a model that discards the Neural subtype, found to be associated with samples with a high content of normal tissue. These samples can be misclassified preventing biological and clinical insights into the different tumor subtypes from coming to light. In this work, we present a model that tackles both the molecular classification of samples and discrimination of those with a high content of normal cells. We performed a transcriptomic in silico analysis on glioblastoma (GBM) samples (n = 810) and tested different criteria to optimize the number of genes needed for molecular classification. We used gene expression of normal brain samples (n = 555) to design an additional gene signature to detect samples with a high normal tissue content. Microdissection samples of different structures within GBM (n = 122) have been used to validate the final model. Finally, the model was tested in a cohort of 43 patients and confirmed by histology. Based on the expression of 20 genes, our model is able to discriminate samples with a high content of normal tissue and to classify the remaining ones. We have shown that taking into consideration normal cells can prevent errors in the classification and the subsequent misinterpretation of the results. Moreover, considering only samples with a low content of normal cells, we found an association between the complexity of the samples and survival for the three molecular subtypes.

scholarly journals Molecular Classification and Tumor Microenvironment Characterization of Gallbladder Cancer by Comprehensive Genomic and Transcriptomic Analysis

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 733
Author(s):  
Nobutaka Ebata ◽  
Masashi Fujita ◽  
Shota Sasagawa ◽  
Kazuhiro Maejima ◽  
Yuki Okawa ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Gallbladder Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Molecular Classification ◽  
Mesenchymal Transition ◽  
Elevated Expression ◽  
Fresh Frozen ◽  
Therapeutic Decision Making

Gallbladder cancer (GBC), a rare but lethal disease, is often diagnosed at advanced stages. So far, molecular characterization of GBC is insufficient, and a comprehensive molecular portrait is warranted to uncover new targets and classify GBC. We performed a transcriptome analysis of both coding and non-coding RNAs from 36 GBC fresh-frozen samples. The results were integrated with those of comprehensive mutation profiling based on whole-genome or exome sequencing. The clustering analysis of RNA-seq data facilitated the classification of GBCs into two subclasses, characterized by high or low expression levels of TME (tumor microenvironment) genes. A correlation was observed between gene expression and pathological immunostaining. TME-rich tumors showed significantly poor prognosis and higher recurrence rate than TME-poor tumors. TME-rich tumors showed overexpression of genes involved in epithelial-to-mesenchymal transition (EMT) and inflammation or immune suppression, which was validated by immunostaining. One non-coding RNA, miR125B1, exhibited elevated expression in stroma-rich tumors, and miR125B1 knockout in GBC cell lines decreased its invasion ability and altered the EMT pathway. Mutation profiles revealed TP53 (47%) as the most commonly mutated gene, followed by ELF3 (13%) and ARID1A (11%). Mutations of ARID1A, ERBB3, and the genes related to the TGF-β signaling pathway were enriched in TME-rich tumors. This comprehensive analysis demonstrated that TME, EMT, and TGF-β pathway alterations are the main drivers of GBC and provides a new classification of GBCs that may be useful for therapeutic decision-making.

scholarly journals MultiKOC: Multi-One-Class Classifier Based K-Means Clustering

Algorithms ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 134
Author(s):  
Loai Abdallah ◽  
Murad Badarna ◽  
Waleed Khalifa ◽  
Malik Yousef
Keyword(s):  
Clustering Algorithm ◽  
Main Idea ◽  
Molecular Classification ◽  
Positive Sample ◽  
Classification Problems ◽  
Multiple Cancer ◽  
Multiple Tumor ◽  
One Class Classifier ◽  
The Given

In the computational biology community there are many biological cases that are considered as multi-one-class classification problems. Examples include the classification of multiple tumor types, protein fold recognition and the molecular classification of multiple cancer types. In all of these cases the real world appropriately characterized negative cases or outliers are impractical to achieve and the positive cases might consist of different clusters, which in turn might lead to accuracy degradation. In this paper we present a novel algorithm named MultiKOC multi-one-class classifiers based K-means to deal with this problem. The main idea is to execute a clustering algorithm over the positive samples to capture the hidden subdata of the given positive data, and then building up a one-class classifier for every cluster member’s examples separately: in other word, train the OC classifier on each piece of subdata. For a given new sample, the generated classifiers are applied. If it is rejected by all of those classifiers, the given sample is considered as a negative sample, otherwise it is a positive sample. The results of MultiKOC are compared with the traditional one-class, multi-one-class, ensemble one-classes and two-class methods, yielding a significant improvement over the one-class and like the two-class performance.

scholarly journals CNN architecture comparison for radio galaxy classification

2021 ◽  
Vol 503 (2) ◽  
pp. 1828-1846
Author(s):  
Burger Becker ◽  
Mattia Vaccari ◽  
Matthew Prescott ◽  
Trienko Grobler
Keyword(s):  
Comparative Study ◽  
Galaxy Evolution ◽  
Radio Galaxy ◽  
Recognition Performance ◽  
Model Complexity ◽  
Great Promise ◽  
Radio Sources ◽  
Morphological Classification ◽  
Computational Performance

ABSTRACT The morphological classification of radio sources is important to gain a full understanding of galaxy evolution processes and their relation with local environmental properties. Furthermore, the complex nature of the problem, its appeal for citizen scientists, and the large data rates generated by existing and upcoming radio telescopes combine to make the morphological classification of radio sources an ideal test case for the application of machine learning techniques. One approach that has shown great promise recently is convolutional neural networks (CNNs). Literature, however, lacks two major things when it comes to CNNs and radio galaxy morphological classification. First, a proper analysis of whether overfitting occurs when training CNNs to perform radio galaxy morphological classification using a small curated training set is needed. Secondly, a good comparative study regarding the practical applicability of the CNN architectures in literature is required. Both of these shortcomings are addressed in this paper. Multiple performance metrics are used for the latter comparative study, such as inference time, model complexity, computational complexity, and mean per class accuracy. As part of this study, we also investigate the effect that receptive field, stride length, and coverage have on recognition performance. For the sake of completeness, we also investigate the recognition performance gains that we can obtain by employing classification ensembles. A ranking system based upon recognition and computational performance is proposed. MCRGNet, Radio Galaxy Zoo, and ConvXpress (novel classifier) are the architectures that best balance computational requirements with recognition performance.

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