Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 185
Filtrar
1.
Cell ; 185(1): 184-203.e19, 2022 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-34963056

RESUMO

Cancers display significant heterogeneity with respect to tissue of origin, driver mutations, and other features of the surrounding tissue. It is likely that individual tumors engage common patterns of the immune system-here "archetypes"-creating prototypical non-destructive tumor immune microenvironments (TMEs) and modulating tumor-targeting. To discover the dominant immune system archetypes, the University of California, San Francisco (UCSF) Immunoprofiler Initiative (IPI) processed 364 individual tumors across 12 cancer types using standardized protocols. Computational clustering of flow cytometry and transcriptomic data obtained from cell sub-compartments uncovered dominant patterns of immune composition across cancers. These archetypes were profound insofar as they also differentiated tumors based upon unique immune and tumor gene-expression patterns. They also partitioned well-established classifications of tumor biology. The IPI resource provides a template for understanding cancer immunity as a collection of dominant patterns of immune organization and provides a rational path forward to learn how to modulate these to improve therapy.


Assuntos
Censos , Neoplasias/genética , Neoplasias/imunologia , Transcriptoma/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais , Análise por Conglomerados , Estudos de Coortes , Biologia Computacional/métodos , Citometria de Fluxo/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/classificação , Neoplasias/patologia , RNA-Seq/métodos , São Francisco , Universidades
2.
Mol Cell ; 78(1): 96-111.e6, 2020 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-32105612

RESUMO

Current models suggest that chromosome domains segregate into either an active (A) or inactive (B) compartment. B-compartment chromatin is physically separated from the A compartment and compacted by the nuclear lamina. To examine these models in the developmental context of C. elegans embryogenesis, we undertook chromosome tracing to map the trajectories of entire autosomes. Early embryonic chromosomes organized into an unconventional barbell-like configuration, with two densely folded B compartments separated by a central A compartment. Upon gastrulation, this conformation matured into conventional A/B compartments. We used unsupervised clustering to uncover subpopulations with differing folding properties and variable positioning of compartment boundaries. These conformations relied on tethering to the lamina to stretch the chromosome; detachment from the lamina compacted, and allowed intermingling between, A/B compartments. These findings reveal the diverse conformations of early embryonic chromosomes and uncover a previously unappreciated role for the lamina in systemic chromosome stretching.


Assuntos
Caenorhabditis elegans/genética , Cromossomos/química , Lâmina Nuclear/fisiologia , Animais , Caenorhabditis elegans/embriologia , Cromossomos/ultraestrutura , Embrião não Mamífero/ultraestrutura , Gastrulação/genética , Hibridização in Situ Fluorescente , Conformação Molecular
3.
Proc Natl Acad Sci U S A ; 121(33): e2403771121, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39110730

RESUMO

Complex systems are typically characterized by intricate internal dynamics that are often hard to elucidate. Ideally, this requires methods that allow to detect and classify in an unsupervised way the microscopic dynamical events occurring in the system. However, decoupling statistically relevant fluctuations from the internal noise remains most often nontrivial. Here, we describe "Onion Clustering": a simple, iterative unsupervised clustering method that efficiently detects and classifies statistically relevant fluctuations in noisy time-series data. We demonstrate its efficiency by analyzing simulation and experimental trajectories of various systems with complex internal dynamics, ranging from the atomic- to the microscopic-scale, in- and out-of-equilibrium. The method is based on an iterative detect-classify-archive approach. In a similar way as peeling the external (evident) layer of an onion reveals the internal hidden ones, the method performs a first detection/classification of the most populated dynamical environment in the system and of its characteristic noise. The signal of such dynamical cluster is then removed from the time-series data and the remaining part, cleared-out from its noise, is analyzed again. At every iteration, the detection of hidden dynamical subdomains is facilitated by an increasing (and adaptive) relevance-to-noise ratio. The process iterates until no new dynamical domains can be uncovered, revealing, as an output, the number of clusters that can be effectively distinguished/classified in a statistically robust way as a function of the time-resolution of the analysis. Onion Clustering is general and benefits from clear-cut physical interpretability. We expect that it will help analyzing a variety of complex dynamical systems and time-series data.

4.
Proc Natl Acad Sci U S A ; 121(37): e2400002121, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39226348

RESUMO

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study.


Assuntos
Análise de Célula Única , Análise de Célula Única/métodos , Análise por Conglomerados , Humanos , Análise de Sequência de RNA/métodos , Animais , Algoritmos , RNA/genética , Perfilação da Expressão Gênica/métodos , RNA-Seq/métodos
5.
BMC Bioinformatics ; 25(1): 42, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273275

RESUMO

BACKGROUND: The clustering of immune repertoire data is challenging due to the computational cost associated with a very large number of pairwise sequence comparisons. To overcome this limitation, we developed Anchor Clustering, an unsupervised clustering method designed to identify similar sequences from millions of antigen receptor gene sequences. First, a Point Packing algorithm is used to identify a set of maximally spaced anchor sequences. Then, the genetic distance of the remaining sequences to all anchor sequences is calculated and transformed into distance vectors. Finally, distance vectors are clustered using unsupervised clustering. This process is repeated iteratively until the resulting clusters are small enough so that pairwise distance comparisons can be performed. RESULTS: Our results demonstrate that Anchor Clustering is faster than existing pairwise comparison clustering methods while providing similar clustering quality. With its flexible, memory-saving strategy, Anchor Clustering is capable of clustering millions of antigen receptor gene sequences in just a few minutes. CONCLUSIONS: This method enables the meta-analysis of immune-repertoire data from different studies and could contribute to a more comprehensive understanding of the immune repertoire data space.


Assuntos
Algoritmos , Receptores de Antígenos , Análise por Conglomerados
6.
J Membr Biol ; 257(1-2): 115-129, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38150051

RESUMO

Lung adenocarcinoma (LUAD) is one of the deadliest malignant tumors worldwide. Transient receptor potential vanilloid (TRPV) channels take pivotal parts in many cancers, but their impact on LUAD remains unexplored. In this study, LUAD samples were classified into two subtypes according to the expression characteristics of TRPV1-6 genes, with LUAD subtype cluster2 exhibiting significantly higher survival rates than cluster1. Subsequently, analysis of differentially expressed genes (DEGs) was performed between cluster1 and cluster2, revealing enrichment of DEGs in channel activity and Ca2+ signaling pathways. We established a protein-protein interaction network based on DEGs and constructed a LUAD prognostic model by using Cox regression analysis based on genes corresponding to 170 protein nodes. The prognostic model demonstrated good predictive ability for patient prognosis, with higher survival rates observed in the low-risk (LR) group. The risk score was validated as an independent prognostic indicator, according to Cox regression analysis. A clinically applicable nomogram was plotted. Immunological analysis indicated that the LR and high-risk (HR) groups had varied proportions of immune cell infiltration. The immunotherapy prediction indicated that LUAD patients in LR group had a greater likelihood to benefit from immune checkpoint blockade therapy. Furthermore, we hypothesized that the expression patterns of feature genes in the LUAD model were related to the sensitivity to lung cancer therapeutic drugs TAS-6417 and Erlotinib. To sum up, our LUAD prognostic model possessed clinical applicability for prognosis and immunotherapy response prediction.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Prognóstico , Adenocarcinoma de Pulmão/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética
7.
Brief Bioinform ; 23(2)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35021202

RESUMO

The cell type identification is among the most important tasks in single-cell RNA-sequencing (scRNA-seq) analysis. Many in silico methods have been developed and can be roughly categorized as either supervised or unsupervised. In this study, we investigated the performances of 8 supervised and 10 unsupervised cell type identification methods using 14 public scRNA-seq datasets of different tissues, sequencing protocols and species. We investigated the impacts of a number of factors, including total amount of cells, number of cell types, sequencing depth, batch effects, reference bias, cell population imbalance, unknown/novel cell type, and computational efficiency and scalability. Instead of merely comparing individual methods, we focused on factors' impacts on the general category of supervised and unsupervised methods. We found that in most scenarios, the supervised methods outperformed the unsupervised methods, except for the identification of unknown cell types. This is particularly true when the supervised methods use a reference dataset with high informational sufficiency, low complexity and high similarity to the query dataset. However, such outperformance could be undermined by some undesired dataset properties investigated in this study, which lead to uninformative and biased reference datasets. In these scenarios, unsupervised methods could be comparable to supervised methods. Our study not only explained the cell typing methods' behaviors under different experimental settings but also provided a general guideline for the choice of method according to the scientific goal and dataset properties. Finally, our evaluation workflow is implemented as a modularized R pipeline that allows future evaluation of new methods. Availability: All the source codes are available at https://github.com/xsun28/scRNAIdent.


Assuntos
Perfilação da Expressão Gênica , Análise de Célula Única , Algoritmos , Análise por Conglomerados , Perfilação da Expressão Gênica/métodos , RNA-Seq , Análise de Sequência de RNA/métodos , Análise de Célula Única/métodos
8.
Brief Bioinform ; 23(4)2022 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-35849048

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common types of cancers and a global health challenge with a low early diagnosis rate and high mortality. The coagulation cascade plays an important role in the tumor immune microenvironment (TME) of HCC. In this study, based on the coagulation pathways collected from the KEGG database, two coagulation-related subtypes were distinguished in HCC patients. We demonstrated the distinct differences in immune characteristics and prognostic stratification between two coagulation-related subtypes. A coagulation-related risk score prognostic model was developed in the Cancer Genome Atlas (TCGA) cohort for risk stratification and prognosis prediction. The predictive values of the coagulation-related risk score in prognosis and immunotherapy were also verified in the TCGA and International Cancer Genome Consortium cohorts. A nomogram was also established to facilitate the clinical use of this risk score and verified its effectiveness using different approaches. Based on these results, we can conclude that there is an obvious correlation between the coagulation and the TME in HCC, and the risk score could serve as a robust prognostic biomarker, provide therapeutic benefits for chemotherapy and immunotherapy and may be helpful for clinical decision making in HCC patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Humanos , Nomogramas , Microambiente Tumoral/genética
9.
Epilepsia ; 65(4): 1092-1106, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38345348

RESUMO

OBJECTIVE: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy. METHODS: Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach. RESULTS: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties. SIGNIFICANCE: Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia do Lobo Temporal , Humanos , Epilepsia do Lobo Temporal/diagnóstico por imagem , Epilepsia do Lobo Temporal/patologia , Imageamento por Ressonância Magnética/métodos , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Lobo Temporal/patologia , Atrofia/patologia , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/patologia , Esclerose/patologia
10.
Cereb Cortex ; 33(7): 3575-3590, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35965076

RESUMO

Brain cartography has expanded substantially over the past decade. In this regard, resting-state functional connectivity (FC) plays a key role in identifying the locations of putative functional borders. However, scant attention has been paid to the dynamic nature of functional interactions in the human brain. Indeed, FC is typically assumed to be stationary across time, which may obscure potential or subtle functional boundaries, particularly in regions with high flexibility and adaptability. In this study, we developed a dynamic FC (dFC)-based parcellation framework, established a new functional human brain atlas termed D-BFA (DFC-based Brain Functional Atlas), and verified its neurophysiological plausibility by stereo-EEG data. As the first dFC-based whole-brain atlas, the proposed D-BFA delineates finer functional boundaries that cannot be captured by static FC, and is further supported by good correspondence with cytoarchitectonic areas and task activation maps. Moreover, the D-BFA reveals the spatial distribution of dynamic variability across the brain and generates more homogenous parcels compared with most alternative parcellations. Our results demonstrate the superiority and practicability of dFC in brain parcellation, providing a new template to exploit brain topographic organization from a dynamic perspective. The D-BFA will be publicly available for download at https://github.com/sliderplm/D-BFA-618.


Assuntos
Encéfalo , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos
11.
BMC Womens Health ; 24(1): 6, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166898

RESUMO

Breast cancer (BC) is a prominent cause of cancer incidence and mortality around the world. Disulfidptosis, a type of cell death, can induce tumor cell death. The purpose of this study was to analyze the potential impact of disulfidptosis-related genes (DRGs) on the prognosis and immune infiltration features of BC. Based on DRGs, we conducted an unsupervised clustering analysis on gene expression data of BC in TCGA-BRCA dataset and identified two BC subtypes, cluster1 and cluster2, with cluster1 showing a higher likelihood of favorable survival. Through immune analysis, we found that cluster1 had lower proportions of infiltration in immune-related cells, including aDCs, DCs, NK_cells, Th2_cells, and Treg. Based on the immunophenoscore (IPS) results, we inferred that cluster1 might benefit more from immune checkpoint inhibitors targeting CTLA-4 and PD1. Targeted small molecule prediction results showed that patients with cluster2 BC might respond better to antagonistic small molecule compounds, including clofazimine, lenalidomide, and epigallocatechin. Differentially expressed genes between the two subtypes were found to be enriched in signaling pathways related to steroid hormone biosynthesis, ovarian steroidogenesis, and neutrophil extracellular trap formation, according to enrichment analyses. In conclusion, this study identified BC subtypes based on DRGs so as to help predict patient prognosis and provide valuable tools for guiding clinical management and precise treatment of BC patients.


Assuntos
Neoplasias da Mama , Inibidores de Checkpoint Imunológico , Imunoterapia , Feminino , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Análise por Conglomerados , Prognóstico , Expressão Gênica
12.
Sensors (Basel) ; 24(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39001059

RESUMO

This paper presents an innovative technique, Advanced Predictor of Electrical Parameters, based on machine learning methods to predict the degradation of electronic components under the effects of radiation. The term degradation refers to the way in which electrical parameters of the electronic components vary with the irradiation dose. This method consists of two sequential steps defined as 'recognition of degradation patterns in the database' and 'degradation prediction of new samples without any kind of irradiation'. The technique can be used under two different approaches called 'pure data driven' and 'model based'. In this paper, the use of Advanced Predictor of Electrical Parameters is shown for bipolar transistors, but the methodology is sufficiently general to be applied to any other component.

13.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542456

RESUMO

This study investigates the roles of mucosal-associated invariant T (MAIT) cells and Vα7.2+/CD161- T cells in skin diseases, focusing on atopic dermatitis. MAIT cells, crucial for bridging innate and adaptive immunity, were analyzed alongside Vα7.2+/CD161- T cells in peripheral blood samples from 14 atopic dermatitis patients and 10 healthy controls. Flow cytometry and machine learning algorithms were employed for a comprehensive analysis. The results indicate a significant decrease in MAIT cells and CD69 subsets in atopic dermatitis, coupled with elevated CD38 and polyfunctional MAIT cells producing TNFα and Granzyme B (TNFα+/GzB+). Vα7.2+/CD161- T cells in atopic dermatitis exhibited a decrease in CD8 and IFNγ-producing subsets but an increase in CD38 activated and IL-22-producing subsets. These results highlight the distinctive features of MAIT cells and Vα7.2+/CD161- T cells and their different roles in the pathogenesis of atopic dermatitis and provide insights into their potential roles in immune-mediated skin diseases.


Assuntos
Dermatite Atópica , Células T Invariantes Associadas à Mucosa , Humanos , Citometria de Fluxo , Fator de Necrose Tumoral alfa , Voluntários Saudáveis
14.
Toxicol Mech Methods ; 34(7): 761-767, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38538091

RESUMO

BACKGROUND: The TGx-DDI biomarker identifies transcripts specifically induced by primary DNA damage. Profiling similarity of TGx-DDI signatures can allow clustering compounds by genotoxic mechanism. This transcriptomics-based approach complements conventional toxicology testing by enhancing mechanistic resolution. METHODS: Unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding (tSNE) were utilized to assess similarity of publicly-available per- and polyfluoroalkyl substances (PFAS) and ToxCast chemicals based on TGx-DDI modulation. TempO-seq transcriptomic data after highest chemical concentrations were analyzed. RESULTS: Clustering discriminated between genotoxic and non-genotoxic compounds while drawing similarity among chemicals with shared mechanisms. PFAS largely clustered distinctly from classical mutagens. However, dynamic range across PFAS types and durations indicated variable potential for DNA damage. tSNE visualization reinforced phenotypic groupings, with genotoxins clustering separately from non-DNA damaging agents. DISCUSSION: Unsupervised learning approaches applied to TGx-DDI profiles effectively categorizes chemical genotoxicity potential, aiding elucidation of biological response pathways. This transcriptomics-based strategy gives further insight into the role and effect of individual TGx-DDI biomarker genes and complements existing assays by enhancing mechanistic resolution. Overall, TGx-DDI biomarker profiling holds promise for predictive safety screening.


Assuntos
Dano ao DNA , Testes de Mutagenicidade , Mutagênicos , Mutagênicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Perfilação da Expressão Gênica , Transcriptoma/efeitos dos fármacos , Humanos , Análise por Conglomerados , Animais , Fluorocarbonos/toxicidade
15.
J Viral Hepat ; 30(2): 116-128, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36355440

RESUMO

Liver cirrhosis has been increasingly diagnosed at an early stage owing to the non-invasive diagnostic techniques. However, it is difficult to identify patients at high risk of disease progression. Screening cirrhotic patients with poor prognosis who are most in need of surveillance is still challenging. Gene expression data GSE15654 and GSE14520 were downloaded for performing unsupervised clustering analysis. The prognostic differences between the different clusters were explored by Cox regression. Integrative analysis of gene expression signature, immune cell enrichments and clinical characterization was performed for different clusters. Two distinctive subclasses were identified in HCV-related GSE15654, and Kaplan-Meier analysis indicated that subtype 2 had lower survival rates than subtype 1 (p = 0.0399). Further analysis revealed subtype 2 had a higher density of follicular T helper cells, resting natural killer cells and M0, M2 macrophages while subtype 1 with a higher fraction of naive B cells, memory B cells, resting memory CD 4 T cells, activated natural killer cells and monocytes. 226 differentially expressed genes were identified between the two subtypes, and Reactome analysis showed the mainly enriched pathways were biological oxidations and fatty acid metabolism. Five hub genes (AKT1, RPS16, CDC42, CCND1 and PCBP2) and three significant modules were extracted from the PPI network. The results were validated in HBV-related GSE14520 cohort. We identified two subtypes of patients with different prognosis for hepatitis C-related early-stage liver cirrhosis. Bioinformatics analysis of the gene expression and immune cell profile may provide fresh insight into understanding the prognosis difference.


Assuntos
Perfilação da Expressão Gênica , Cirrose Hepática , Humanos , Perfilação da Expressão Gênica/métodos , Cirrose Hepática/diagnóstico , Cirrose Hepática/genética , Transcriptoma , Prognóstico , Análise em Microsséries , Proteínas de Ligação a RNA/genética
16.
Rheumatology (Oxford) ; 62(7): 2574-2584, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-36308437

RESUMO

OBJECTIVES: To leverage the high clinical heterogeneity of systemic lupus erythematosus (SLE), we developed and validated a new stratification scheme by integrating genome-scale transcriptomic profiles to identify patient subtypes sharing similar transcriptomic markers and drug targets. METHODS: A normalized compendium of transcription profiles was created from peripheral blood mononuclear cells (PBMCs) of 1046 SLE patients and 86 healthy controls (HCs), covering an intersection of 13 689 genes from six microarray datasets. Upregulated differentially expressed genes were subjected to functional and network analysis in which samples were grouped using unsupervised clustering to identify patient subtypes. Then, clustering stability was evaluated by the stratification of six integrated RNA-sequencing datasets using the same method. Finally, the Xgboost classifier was applied to the independent datasets to identify factors associated with treatment outcomes. RESULTS: Based on 278 upregulated DEGs of the transcript profiles, SLE patients were classified into three subtypes (subtype A-C) each with distinct molecular and cellular signatures. Neutrophil activation-related pathways were markedly activated in subtype A (named NE-driving), whereas lymphocyte and IFN-related pathways were more enriched in subtype B (IFN-driving). As the most severe subtype, subtype C [NE-IFN-dual-driving (Dual-driving)] shared functional mechanisms with both NE-driving and IFN-driving, which was closely associated with clinical features and could be used to predict the responses of treatment. CONCLUSION: We developed the largest cohesive SLE transcriptomic compendium for deep stratification using the most comprehensive microarray and RNA sequencing datasets to date. This result could guide future design of molecular diagnosis and the development of stratified therapy for SLE patients.


Assuntos
Lúpus Eritematoso Sistêmico , Transcriptoma , Humanos , Leucócitos Mononucleares/metabolismo , Perfilação da Expressão Gênica/métodos , Análise em Microsséries , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/genética
17.
Transfusion ; 63(12): 2234-2247, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37861272

RESUMO

BACKGROUND: Managing Canada's immunoglobulin (Ig) product resource allocation is challenging due to increasing demand, high expenditure, and global shortages. Detection of groups with high utilization rates can help with resource planning for Ig products. This study aims to uncover utilization subgroups among the Ig recipients using electronic health records (EHRs). METHODS: The study included all Ig recipients (intravenous or subcutaneous) in Calgary from 2014 to 2020, and their EHR data, including blood inventory, recipient demographics, and laboratory test results, were analyzed. Patient clusters were derived based on patient characteristics and laboratory test data using K-means clustering. Clusters were interpreted using descriptive analyses and visualization techniques. RESULTS: Among 4112 recipients, six clusters were identified. Clusters 1 and 2 comprised 408 (9.9%) and 1272 (30.9%) patients, respectively, contributing to 62.2% and 27.1% of total Ig utilization. Cluster 3 included 1253 (30.5%) patients, with 86.4% of infusions administered in an inpatient setting. Cluster 4, comprising 1034 (25.1%) patients, had a median age of 4 years, while clusters 2-6 were adults with median ages of 46-60. Cluster 5 had 62 (1.5%) patients, with 77.3% infusions occurring in emergency departments. Cluster 6 contained 83 (2.0%) patients receiving subcutaneous Ig treatments. CONCLUSION: The results identified data-driven segmentations of patients with high Ig utilization rates and patients with high risk for short-term inpatient use. Our report is the first on EHR data-driven clustering of Ig utilization patterns. The findings hold the potential to inform demand forecasting and resource allocation decisions during shortages of Ig products.


Assuntos
Registros Eletrônicos de Saúde , Aprendizado de Máquina não Supervisionado , Adulto , Humanos , Pré-Escolar , Imunoglobulinas , Pacientes Internados
18.
Environ Sci Technol ; 57(46): 18116-18126, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-37159837

RESUMO

Dissolved organic matter (DOM) is a complex mixture of thousands of natural molecules that undergo constant transformation in the environment, such as sunlight induced photochemical reactions. Despite molecular level resolution from ultrahigh resolution mass spectrometry (UHRMS), trends of mass peak intensities are currently the only way to follow photochemically induced molecular changes in DOM. Many real-world relationships and temporal processes can be intuitively modeled using graph data structures (networks). Graphs enhance the potential and value of AI applications by adding context and interconnections allowing the uncovering of hidden or unknown relationships in data sets. We use a temporal graph model and link prediction to identify transformations of DOM molecules in a photo-oxidation experiment. Our link prediction algorithm simultaneously considers educt removal and product formation for molecules linked by predefined transformation units (oxidation, decarboxylation, etc.). The transformations are further weighted by the extent of intensity change and clustered on the graph structure to identify groups of similar reactivity. The temporal graph is capable of identifying relevant molecules subject to similar reactions and enabling to study their time course. Our approach overcomes previous data evaluation limitations for mechanistic studies of DOM and leverages the potential of temporal graphs to study DOM reactivity by UHRMS.


Assuntos
Matéria Orgânica Dissolvida , Luz Solar , Espectrometria de Massas , Oxirredução
19.
Environ Res ; 216(Pt 2): 114519, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36252833

RESUMO

Soil attributes and their environmental drivers exhibit different patterns in different geographical directions, along with distinct regional characteristics, which may have important effects on substance migration and transformation such as organic matter and soil elements or the environmental impacts of pollutants. Therefore, regional soil characteristics should be considered in the process of regionalization for environmental management. However, no comprehensive evaluation or systematic classification of the natural soil environment has been established for China. Here, we established an index system for natural soil environmental regionalization (NSER) by combining literature data obtained based on bibliometrics with the analytic hierarchy process (AHP). Based on the index system, we collected spatial distribution data for 14 indexes at the national scale. In addition, three clustering algorithms-self-organizing feature mapping (SOFM), fuzzy c-means (FCM) and k-means (KM)-were used to classify and define the natural soil environment. We imported four cluster validity indexes (CVI) to evaluate different models: Davies-Bouldin index (DB), Silhouette index (Sil) and Calinski-Harabasz index (CH) for FCM and KM, clustering quality index (CQI) for SOFM. Analysis and comparison of the results showed that when the number of clusters was 13, the FCM clustering algorithm achieved the optimal clustering results (DB = 1.16, Sil = 0.78, CH = 6.77 × 106), allowing the natural soil environment of China to be divided into 12 regions with distinct characteristics. Our study provides a set of comprehensive scientific research methods for regionalization research based on spatial data, it has important reference value for improving soil environmental management based on local conditions in China.


Assuntos
Algoritmos , Solo , Análise por Conglomerados , Geografia , China , Lógica Fuzzy
20.
Sensors (Basel) ; 23(3)2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36772629

RESUMO

Autonomous unmanned aerial vehicles (UAVs) have attracted increasing academic and industrial attention during the last decade. Using drones have broad benefits in diverse areas, such as civil and military applications, aerial photography and videography, mapping and surveying, agriculture, and disaster management. However, the recent development and innovation in the field of drone (UAV) technology have led to malicious usage of the technology, including the penetration of secure areas (such as airports) and serving terrorist attacks. Autonomous weapon systems might use drone swarms to perform more complex military tasks. Utilizing a large number of drones, simultaneously increases the risk and the reliability of the mission in terms of redundancy, survivability, scalability, and the quality of autonomous performance in a complex environment. This research suggests a new approach for drone swarm characterization and detection using RF signals analysis and various machine learning methods. While most of the existing drone detection and classification methods are typically related to a single drone classification, using supervised approaches, this research work proposes an unsupervised approach for drone swarm characterization. The proposed method utilizes the different radio frequency (RF) signatures of the drone's transmitters. Various kinds of frequency transform, such as the continuous, discrete, and wavelet scattering transform, have been applied to extract RF features from the radio frequency fingerprint, which have then been used as input for the unsupervised classifier. To reduce the input data dimension, we suggest using unsupervised approaches such as Principal component analysis (PCA), independent component analysis (ICA), uniform manifold approximation and projection (UMAP), and the t-distributed symmetric neighbor embedding (t-SNE) algorithms. The proposed clustering approach is based on common unsupervised methods, including K-means, mean shift, and X-means algorithms. The proposed approach has been evaluated using self-built and common drone swarm datasets. The results demonstrate a classification accuracy of about 95% under additive Gaussian white noise with different levels of SNR.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA