130 research outputs found
ClinicLens: Visual Analytics for Exploring and Optimizing the Testing Capacity of Clinics given Uncertainty
Clinic testing plays a critical role in containing infectious diseases such
as COVID-19. However, one of the key research questions in fighting such
pandemics is how to optimize testing capacities across clinics. In particular,
domain experts expect to know exactly how to adjust the features that may
affect testing capacities, given that dynamics and uncertainty make this a
highly challenging problem. Hence, as a tool to support both policymakers and
clinicians, we collaborated with domain experts to build ClinicLens, an
interactive visual analytics system for exploring and optimizing the testing
capacities of clinics. ClinicLens houses a range of features based on an
aggregated set of COVID-19 data. It comprises Back-end Engine and Front-end
Visualization that take users through an iterative exploration chain of
extracting, training, and predicting testing-sensitive features and visual
representations. It also combines AI4VIS and visual analytics to demonstrate
how a clinic might optimize its testing capacity given the impacts of a range
of features. Three qualitative case studies along with feedback from
subject-matter experts validate that ClinicLens is both a useful and effective
tool for exploring the trends in COVID-19 and optimizing clinic testing
capacities across regions. The entire approach has been open-sourced online:
https://github.com/YuDong5018/clinic-lens
Considerations for Treatment Development in Rhabdomyosarcoma: In Vitro Assessment of Novel DNA Binding Drugs
Relational Autoencoder for Feature Extraction
Feature extraction becomes increasingly important as data grows high
dimensional. Autoencoder as a neural network based feature extraction method
achieves great success in generating abstract features of high dimensional
data. However, it fails to consider the relationships of data samples which may
affect experimental results of using original and new features. In this paper,
we propose a Relation Autoencoder model considering both data features and
their relationships. We also extend it to work with other major autoencoder
models including Sparse Autoencoder, Denoising Autoencoder and Variational
Autoencoder. The proposed relational autoencoder models are evaluated on a set
of benchmark datasets and the experimental results show that considering data
relationships can generate more robust features which achieve lower
construction loss and then lower error rate in further classification compared
to the other variants of autoencoders.Comment: IJCNN-201
Inferring Actual Treatment Pathways from Patient Records
Treatment pathways are step-by-step plans outlining the recommended medical
care for specific diseases; they get revised when different treatments are
found to improve patient outcomes. Examining health records is an important
part of this revision process, but inferring patients' actual treatments from
health data is challenging due to complex event-coding schemes and the absence
of pathway-related annotations. This study aims to infer the actual treatment
steps for a particular patient group from administrative health records (AHR) -
a common form of tabular healthcare data - and address several technique- and
methodology-based gaps in treatment pathway-inference research. We introduce
Defrag, a method for examining AHRs to infer the real-world treatment steps for
a particular patient group. Defrag learns the semantic and temporal meaning of
healthcare event sequences, allowing it to reliably infer treatment steps from
complex healthcare data. To our knowledge, Defrag is the first
pathway-inference method to utilise a neural network (NN), an approach made
possible by a novel, self-supervised learning objective. We also developed a
testing and validation framework for pathway inference, which we use to
characterise and evaluate Defrag's pathway inference ability and compare
against baselines. We demonstrate Defrag's effectiveness by identifying
best-practice pathway fragments for breast cancer, lung cancer, and melanoma in
public healthcare records. Additionally, we use synthetic data experiments to
demonstrate the characteristics of the Defrag method, and to compare Defrag to
several baselines where it significantly outperforms non-NN-based methods.
Defrag significantly outperforms several existing pathway-inference methods and
offers an innovative and effective approach for inferring treatment pathways
from AHRs. Open-source code is provided to encourage further research in this
area
Inter-Platform comparability of microarrays in acute lymphoblastic leukemia
BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS) rates improving from <10% in 1970 to >80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21)[TEL-AML1], t(4;11)[MLL-AF4], t(9;22)[BCR-ABL], and t(1;19)[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. RESULTS: We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors for prognostic variables. We have also been able to validate the gene predictors with high accuracy using an independent dataset generated on cDNA arrays. CONCLUSION: Interarray comparisons such as this one will further enhance the ability to integrate data from several generations of microarray experiments and will help to break down barriers to the assimilation of existing datasets into a comprehensive data pool
MINER: exploratory analysis of gene interaction networks by machine learning from expression data
<p>Abstract</p> <p>Background</p> <p>The reconstruction of gene regulatory networks from high-throughput "omics" data has become a major goal in the modelling of living systems. Numerous approaches have been proposed, most of which attempt only "one-shot" reconstruction of the whole network with no intervention from the user, or offer only simple correlation analysis to infer gene dependencies.</p> <p>Results</p> <p>We have developed MINER (Microarray Interactive Network Exploration and Representation), an application that combines multivariate non-linear tree learning of individual gene regulatory dependencies, visualisation of these dependencies as both trees and networks, and representation of known biological relationships based on common Gene Ontology annotations. MINER allows biologists to explore the dependencies influencing the expression of individual genes in a gene expression data set in the form of decision, model or regression trees, using their domain knowledge to guide the exploration and formulate hypotheses. Multiple trees can then be summarised in the form of a gene network diagram. MINER is being adopted by several of our collaborators and has already led to the discovery of a new significant regulatory relationship with subsequent experimental validation.</p> <p>Conclusion</p> <p>Unlike most gene regulatory network inference methods, MINER allows the user to start from genes of interest and build the network gene-by-gene, incorporating domain expertise in the process. This approach has been used successfully with RNA microarray data but is applicable to other quantitative data produced by high-throughput technologies such as proteomics and "next generation" DNA sequencing.</p
Review of innovative immersive technologies for healthcare applications
Immersive technologies, including virtual reality (VR), augmented reality (AR), and mixed reality (MR), can connect people using enhanced data visualizations to better involve stakeholders as integral members of the process. Immersive technologies have started to change the research on multidimensional genomic data analysis for disease diagnostics and treatments. Immersive technologies
are highlighted in some research for health and clinical needs, especially for precision medicine innovation. The use of immersive technology for genomic data analysis has recently received attention from the research community. Genomic data analytics research seeks to integrate immersive technologies to build more natural human-computer interactions that allow better perception engagements. Immersive technologies, especially VR, help humans perceive the digital world as real and give learning output with lower performance errors and higher accuracy. However, there are limited reviews about immersive technologies used in healthcare and genomic data analysis with specific digital health applications. This paper contributes a comprehensive review of using immersive technologies for digital health applications, including patient-centric applications, medical domain education, and data analysis, especially genomic data visual analytics. We highlight the evolution of a visual analysis using VR as a case study for how
immersive technologies step, can by step, move into the genomic data analysis domain. The discussion and conclusion summarize the current immersive technology applications’ usability, innovation, and future work in the healthcare domain, and digital health data visual analytics
Alternative propulsor for mobile transportation and technological machines wood complex
Лесные машины, оборудованные альтернативным движителем, способны передвигаться по любым типам поверхностей (подготовленным дорогам, пахоте, болоту, песку, заснеженной местности и т.д.) с минимальным негативным воздействием.Forestry machines equipped alternative propulsors are capable to move on any types of land surfaces (the prepared roads, plowed land, bog, the sand, snow-covered land and etc.) with the minimal negative influence
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The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias.
BACKGROUND: The Ras-association family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-association (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1-10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples. RESULTS: COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC). CONCLUSION: This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are
A Genome-wide screen identifies frequently methylated genes in haematological and epithelial cancers
<p>Abstract</p> <p>Background</p> <p>Genetic as well as epigenetic alterations are a hallmark of both epithelial and haematological malignancies. High throughput screens are required to identify epigenetic markers that can be useful for diagnostic and prognostic purposes across malignancies.</p> <p>Results</p> <p>Here we report for the first time the use of the MIRA assay (methylated CpG island recovery assay) in combination with genome-wide CpG island arrays to identify epigenetic molecular markers in childhood acute lymphoblastic leukemia (ALL) on a genome-wide scale. We identified 30 genes demonstrating methylation frequencies of ≥25% in childhood ALL, nine genes showed significantly different methylation frequencies in B vs T-ALL. For majority of the genes expression could be restored in methylated leukemia lines after treatment with 5-azaDC. Forty-four percent of the genes represent targets of the polycomb complex. In chronic myeloid leukemia (CML) two of the genes, (<it>TFAP2A </it>and <it>EBF2)</it>, demonstrated increased methylation in blast crisis compared to chronic phase (P < 0.05). Furthermore hypermethylation of an autophagy related gene <it>ATG16L2 </it>was associated with poorer prognosis in terms of molecular response to Imatinib treatment. Lastly we demonstrated that ten of these genes were also frequently methylated in common epithelial cancers.</p> <p>Conclusion</p> <p>In summary we have identified a large number of genes showing frequent methylation in childhood ALL, methylation status of two of these genes is associated with advanced disease in CML and methylation status of another gene is associated with prognosis. In addition a subset of these genes may act as epigenetic markers across hematological malignancies as well as common epithelial cancers.</p
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