9,051 research outputs found
Regulatory T cells in melanoma revisited by a computational clustering of FOXP3+ T cell subpopulations
CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Treg). FOXP3+ T cells are reported to be increased in tumour-bearing patients or animals, and considered to suppress anti-tumour immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation, and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumour immunity, but the arbitrariness and complexity of manual gating have complicated the issue. Here we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analysing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally-identified FOXP3+ subpopulation included not only classical FOXP3high Treg but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analysed an independent dataset, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Treg
A computational pipeline for the diagnosis of CVID patients
Common variable immunodeficiency (CVID) is one of the most frequently diagnosed primary antibody deficiencies (PADs), a group of disorders characterized by a decrease in one or more immunoglobulin (sub) classes and/or impaired antibody responses caused by inborn defects in B cells in the absence of other major immune defects. CVID patients suffer from recurrent infections and disease-related, non-infectious, complications such as autoimmune manifestations, lymphoproliferation, and malignancies. A timely diagnosis is essential for optimal follow-up and treatment. However, CVID is by definition a diagnosis of exclusion, thereby covering a heterogeneous patient population and making it difficult to establish a definite diagnosis. To aid the diagnosis of CVID patients, and distinguish them from other PADs, we developed an automated machine learning pipeline which performs automated diagnosis based on flow cytometric immunophenotyping. Using this pipeline, we analyzed the immunophenotypic profile in a pediatric and adult cohort of 28 patients with CVID, 23 patients with idiopathic primary hypogammaglobulinemia, 21 patients with IgG subclass deficiency, six patients with isolated IgA deficiency, one patient with isolated IgM deficiency, and 100 unrelated healthy controls. Flow cytometry analysis is traditionally done by manual identification of the cell populations of interest. Yet, this approach has severe limitations including subjectivity of the manual gating and bias toward known populations. To overcome these limitations, we here propose an automated computational flow cytometry pipeline that successfully distinguishes CVID phenotypes from other PADs and healthy controls. Compared to the traditional, manual analysis, our pipeline is fully automated, performing automated quality control and data pre-processing, automated population identification (gating) and deriving features from these populations to build a machine learning classifier to distinguish CVID from other PADs and healthy controls. This results in a more reproducible flow cytometry analysis, and improves the diagnosis compared to manual analysis: our pipelines achieve on average a balanced accuracy score of 0.93 (+/- 0.07), whereas using the manually extracted populations, an averaged balanced accuracy score of 0.72 (+/- 0.23) is achieved
MTDeep: Boosting the Security of Deep Neural Nets Against Adversarial Attacks with Moving Target Defense
Present attack methods can make state-of-the-art classification systems based
on deep neural networks misclassify every adversarially modified test example.
The design of general defense strategies against a wide range of such attacks
still remains a challenging problem. In this paper, we draw inspiration from
the fields of cybersecurity and multi-agent systems and propose to leverage the
concept of Moving Target Defense (MTD) in designing a meta-defense for
'boosting' the robustness of an ensemble of deep neural networks (DNNs) for
visual classification tasks against such adversarial attacks. To classify an
input image, a trained network is picked randomly from this set of networks by
formulating the interaction between a Defender (who hosts the classification
networks) and their (Legitimate and Malicious) users as a Bayesian Stackelberg
Game (BSG). We empirically show that this approach, MTDeep, reduces
misclassification on perturbed images in various datasets such as MNIST,
FashionMNIST, and ImageNet while maintaining high classification accuracy on
legitimate test images. We then demonstrate that our framework, being the first
meta-defense technique, can be used in conjunction with any existing defense
mechanism to provide more resilience against adversarial attacks that can be
afforded by these defense mechanisms. Lastly, to quantify the increase in
robustness of an ensemble-based classification system when we use MTDeep, we
analyze the properties of a set of DNNs and introduce the concept of
differential immunity that formalizes the notion of attack transferability.Comment: Accepted to the Conference on Decision and Game Theory for Security
(GameSec), 201
On the hierarchical classification of G Protein-Coupled Receptors
Motivation: G protein-coupled receptors (GPCRs) play an important role in many physiological systems by transducing an extracellular signal into an intracellular response. Over 50% of all marketed drugs are targeted towards a GPCR. There is considerable interest in developing an algorithm that could effectively predict the function of a GPCR from its primary sequence. Such an algorithm is useful not only in identifying novel GPCR sequences but in characterizing the interrelationships between known GPCRs.
Results: An alignment-free approach to GPCR classification has been developed using techniques drawn from data mining and proteochemometrics. A dataset of over 8000 sequences was constructed to train the algorithm. This represents one of the largest GPCR datasets currently available. A predictive algorithm was developed based upon the simplest reasonable numerical representation of the protein's physicochemical properties. A selective top-down approach was developed, which used a hierarchical classifier to assign sequences to subdivisions within the GPCR hierarchy. The predictive performance of the algorithm was assessed against several standard data mining classifiers and further validated against Support Vector Machine-based GPCR prediction servers. The selective top-down approach achieves significantly higher accuracy than standard data mining methods in almost all cases
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The robust selection of predictive genes via a simple classifier
Identifying genes that direct the mechanism of a disease from expression data is extremely useful in understanding how that mechanism works.
This in turn may lead to better diagnoses and potentially can lead to a cure for that disease. This task becomes extremely challenging when the
data are characterised by only a small number of samples and a high number of dimensions, as it is often the case with gene expression data.
Motivated by this challenge, we present a general framework that focuses on simplicity and data perturbation. These are the keys for the robust
identification of the most predictive features in such data. Within this framework, we propose a simple selective na¨ıve Bayes classifier discovered using a global search technique, and combine it with data perturbation to
increase its robustness to small sample sizes.
An extensive validation of the method was carried out using two applied datasets from the field of microarrays and a simulated dataset, all
confounded by small sample sizes and high dimensionality. The method has been shown capable of identifying genes previously confirmed or associated with prostate cancer and viral infections
ProtNN: Fast and Accurate Nearest Neighbor Protein Function Prediction based on Graph Embedding in Structural and Topological Space
Studying the function of proteins is important for understanding the
molecular mechanisms of life. The number of publicly available protein
structures has increasingly become extremely large. Still, the determination of
the function of a protein structure remains a difficult, costly, and time
consuming task. The difficulties are often due to the essential role of spatial
and topological structures in the determination of protein functions in living
cells. In this paper, we propose ProtNN, a novel approach for protein function
prediction. Given an unannotated protein structure and a set of annotated
proteins, ProtNN finds the nearest neighbor annotated structures based on
protein-graph pairwise similarities. Given a query protein, ProtNN finds the
nearest neighbor reference proteins based on a graph representation model and a
pairwise similarity between vector embedding of both query and reference
protein-graphs in structural and topological spaces. ProtNN assigns to the
query protein the function with the highest number of votes across the set of k
nearest neighbor reference proteins, where k is a user-defined parameter.
Experimental evaluation demonstrates that ProtNN is able to accurately classify
several datasets in an extremely fast runtime compared to state-of-the-art
approaches. We further show that ProtNN is able to scale up to a whole PDB
dataset in a single-process mode with no parallelization, with a gain of
thousands order of magnitude of runtime compared to state-of-the-art
approaches
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