4,675 research outputs found
Integrative analysis identifies candidate tumor microenvironment and intracellular signaling pathways that define tumor heterogeneity in NF1
Neurofibromatosis type 1 (NF1) is a monogenic syndrome that gives rise to numerous symptoms including cognitive impairment, skeletal abnormalities, and growth of benign nerve sheath tumors. Nearly all NF1 patients develop cutaneous neurofibromas (cNFs), which occur on the skin surface, whereas 40-60% of patients develop plexiform neurofibromas (pNFs), which are deeply embedded in the peripheral nerves. Patients with pNFs have a ~10% lifetime chance of these tumors becoming malignant peripheral nerve sheath tumors (MPNSTs). These tumors have a severe prognosis and few treatment options other than surgery. Given the lack of therapeutic options available to patients with these tumors, identification of druggable pathways or other key molecular features could aid ongoing therapeutic discovery studies. In this work, we used statistical and machine learning methods to analyze 77 NF1 tumors with genomic data to characterize key signaling pathways that distinguish these tumors and identify candidates for drug development. We identified subsets of latent gene expression variables that may be important in the identification and etiology of cNFs, pNFs, other neurofibromas, and MPNSTs. Furthermore, we characterized the association between these latent variables and genetic variants, immune deconvolution predictions, and protein activity predictions
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Artificial Immune Systems - Models, algorithms and applications
Copyright © 2010 Academic Research Publishing Agency.This article has been made available through the Brunel Open Access Publishing Fund.Artificial Immune Systems (AIS) are computational paradigms that belong to the computational intelligence family and are inspired by the biological immune system. During the past decade, they have attracted a lot of interest from researchers aiming to develop immune-based models and techniques to solve complex computational or engineering problems. This work presents a survey of existing AIS models and algorithms with a focus on the last five years.This article is available through the Brunel Open Access Publishing Fun
Wavelet feature extraction and genetic algorithm for biomarker detection in colorectal cancer data
Biomarkers which predict patient’s survival can play an important role in medical diagnosis and
treatment. How to select the significant biomarkers from hundreds of protein markers is a key step in
survival analysis. In this paper a novel method is proposed to detect the prognostic biomarkers ofsurvival in colorectal cancer patients using wavelet analysis, genetic algorithm, and Bayes classifier. One dimensional discrete wavelet transform (DWT) is normally used to reduce the dimensionality of biomedical data. In this study one dimensional continuous wavelet transform (CWT) was proposed to extract the features of colorectal cancer data. One dimensional CWT has no ability to reduce
dimensionality of data, but captures the missing features of DWT, and is complementary part of DWT. Genetic algorithm was performed on extracted wavelet coefficients to select the optimized features, using Bayes classifier to build its fitness function. The corresponding protein markers were
located based on the position of optimized features. Kaplan-Meier curve and Cox regression model 2 were used to evaluate the performance of selected biomarkers. Experiments were conducted on colorectal cancer dataset and several significant biomarkers were detected. A new protein biomarker CD46 was found to significantly associate with survival time
Blood Cell Revolution: Unveiling 11 Distinct Types with ‘Naturalize’ Augmentation
Artificial intelligence (AI) has emerged as a cutting-edge tool, simultaneously accelerating, securing, and enhancing the diagnosis and treatment of patients. An exemplification of this capability is evident in the analysis of peripheral blood smears (PBS). In university medical centers, hematologists routinely examine hundreds of PBS slides daily to validate or correct outcomes produced by advanced hematology analyzers assessing samples from potentially problematic patients. This process may logically lead to erroneous PBC readings, posing risks to patient health. AI functions as a transformative tool, significantly improving the accuracy and precision of readings and diagnoses. This study reshapes the parameters of blood cell classification, harnessing the capabilities of AI and broadening the scope from 5 to 11 specific blood cell categories with the challenging 11-class PBC dataset. This transformation facilitates a more profound exploration of blood cell diversity, surpassing prior constraints in medical image analysis. Our approach combines state-of-the-art deep learning techniques, including pre-trained ConvNets, ViTb16 models, and custom CNN architectures. We employ transfer learning, fine-tuning, and ensemble strategies, such as CBAM and Averaging ensembles, to achieve unprecedented accuracy and interpretability. Our fully fine-tuned EfficientNetV2 B0 model sets a new standard, with a macro-average precision, recall, and F1-score of 91%, 90%, and 90%, respectively, and an average accuracy of 93%. This breakthrough underscores the transformative potential of 11-class blood cell classification for more precise medical diagnoses. Moreover, our groundbreaking “Naturalize” augmentation technique produces remarkable results. The 2K-PBC dataset generated with “Naturalize” boasts a macro-average precision, recall, and F1-score of 97%, along with an average accuracy of 96% when leveraging the fully fine-tuned EfficientNetV2 B0 model. This innovation not only elevates classification performance but also addresses data scarcity and bias in medical deep learning. Our research marks a paradigm shift in blood cell classification, enabling more nuanced and insightful medical analyses. The “Naturalize” technique’s impact extends beyond blood cell classification, emphasizing the vital role of diverse and comprehensive datasets in advancing healthcare applications through deep learning.This work is supported by grant PID2021-126701OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by “ERDF A way of making Europe”, and by grant GIU19/027 funded by the University of the Basque Country UPV/EHU
Deep generative selection models of T and B cell receptor repertoires with soNNia
Subclasses of lymphocytes carry different functional roles to work together
to produce an immune response and lasting immunity. Additionally to these
functional roles, T and B-cell lymphocytes rely on the diversity of their
receptor chains to recognize different pathogens. The lymphocyte subclasses
emerge from common ancestors generated with the same diversity of receptors
during selection processes. Here we leverage biophysical models of receptor
generation with machine learning models of selection to identify specific
sequence features characteristic of functional lymphocyte repertoires and
subrepertoires. Specifically using only repertoire level sequence information,
we classify CD4 and CD8 T-cells, find correlations between receptor
chains arising during selection and identify T-cells subsets that are targets
of pathogenic epitopes. We also show examples of when simple linear classifiers
do as well as more complex machine learning methods
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Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study
BACKGROUND: For virtually every patient with colorectal cancer (CRC), hematoxylin-eosin (HE)-stained tissue slides are available. These images contain quantitative information, which is not routinely used to objectively extract prognostic biomarkers. In the present study, we investigated whether deep convolutional neural networks (CNNs) can extract prognosticators directly from these widely available images.
METHODS AND FINDINGS: We hand-delineated single-tissue regions in 86 CRC tissue slides, yielding more than 100,000 HE image patches, and used these to train a CNN by transfer learning, reaching a nine-class accuracy of >94% in an independent data set of 7,180 images from 25 CRC patients. With this tool, we performed automated tissue decomposition of representative multitissue HE images from 862 HE slides in 500 stage I-IV CRC patients in the The Cancer Genome Atlas (TCGA) cohort, a large international multicenter collection of CRC tissue. Based on the output neuron activations in the CNN, we calculated a "deep stroma score," which was an independent prognostic factor for overall survival (OS) in a multivariable Cox proportional hazard model (hazard ratio [HR] with 95% confidence interval [CI]: 1.99 [1.27-3.12], p = 0.0028), while in the same cohort, manual quantification of stromal areas and a gene expression signature of cancer-associated fibroblasts (CAFs) were only prognostic in specific tumor stages. We validated these findings in an independent cohort of 409 stage I-IV CRC patients from the "Darmkrebs: Chancen der Verhütung durch Screening" (DACHS) study who were recruited between 2003 and 2007 in multiple institutions in Germany. Again, the score was an independent prognostic factor for OS (HR 1.63 [1.14-2.33], p = 0.008), CRC-specific OS (HR 2.29 [1.5-3.48], p = 0.0004), and relapse-free survival (RFS; HR 1.92 [1.34-2.76], p = 0.0004). A prospective validation is required before this biomarker can be implemented in clinical workflows.
CONCLUSIONS: In our retrospective study, we show that a CNN can assess the human tumor microenvironment and predict prognosis directly from histopathological images
Hidden Markov Models for Gene Sequence Classification: Classifying the VSG genes in the Trypanosoma brucei Genome
The article presents an application of Hidden Markov Models (HMMs) for
pattern recognition on genome sequences. We apply HMM for identifying genes
encoding the Variant Surface Glycoprotein (VSG) in the genomes of Trypanosoma
brucei (T. brucei) and other African trypanosomes. These are parasitic protozoa
causative agents of sleeping sickness and several diseases in domestic and wild
animals. These parasites have a peculiar strategy to evade the host's immune
system that consists in periodically changing their predominant cellular
surface protein (VSG). The motivation for using patterns recognition methods to
identify these genes, instead of traditional homology based ones, is that the
levels of sequence identity (amino acid and DNA sequence) amongst these genes
is often below of what is considered reliable in these methods. Among pattern
recognition approaches, HMM are particularly suitable to tackle this problem
because they can handle more naturally the determination of gene edges. We
evaluate the performance of the model using different number of states in the
Markov model, as well as several performance metrics. The model is applied
using public genomic data. Our empirical results show that the VSG genes on T.
brucei can be safely identified (high sensitivity and low rate of false
positives) using HMM.Comment: Accepted article in July, 2015 in Pattern Analysis and Applications,
Springer. The article contains 23 pages, 4 figures, 8 tables and 51
reference
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