1,037 research outputs found
Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy
Circular RNAs (circRNAs) may act as novel cancer biomarkers. However, a genome-wide evaluation of circRNAs in clear cell renal cell carcinoma (ccRCC) has yet to be conducted. Therefore, the objective of this study was to identify and validate circRNAs in ccRCC tissue with a focus to evaluate their potential as prognostic biomarkers. A genome-wide identification of circRNAs in total RNA extracted from ccRCC tissue samples was performed using microarray analysis. Three relevant differentially expressed circRNAs were selected (circEGLN3, circNOX4, and circRHOBTB3), their circular nature was experimentally confirmed, and their expression-along with that of their linear counterparts-was measured in 99 malignant and 85 adjacent normal tissue samples using specifically established RT-qPCR assays. The capacity of circRNAs to discriminate between malignant and adjacent normal tissue samples and their prognostic potential (with the endpoints cancer-specific, recurrence-free, and overall survival) after surgery were estimated by C-statistics, Kaplan-Meier method, univariate and multivariate Cox regression analysis, decision curve analysis, and Akaike and Bayesian information criteria. CircEGLN3 discriminated malignant from normal tissue with 97% accuracy. We generated a prognostic for the three endpoints by multivariate Cox regression analysis that included circEGLN3, circRHOBT3 and linRHOBTB3. The predictive outcome accuracy of the clinical models based on clinicopathological factors was improved in combination with this circRNA-based signature. Bootstrapping as well as Akaike and Bayesian information criteria confirmed the statistical significance and robustness of the combined models. Limitations of this study include its retrospective nature and the lack of external validation. The study demonstrated the promising potential of circRNAs as diagnostic and particularly prognostic biomarkers in ccRCC patients
Machine Learning and Integrative Analysis of Biomedical Big Data.
Recent developments in high-throughput technologies have accelerated the accumulation of massive amounts of omics data from multiple sources: genome, epigenome, transcriptome, proteome, metabolome, etc. Traditionally, data from each source (e.g., genome) is analyzed in isolation using statistical and machine learning (ML) methods. Integrative analysis of multi-omics and clinical data is key to new biomedical discoveries and advancements in precision medicine. However, data integration poses new computational challenges as well as exacerbates the ones associated with single-omics studies. Specialized computational approaches are required to effectively and efficiently perform integrative analysis of biomedical data acquired from diverse modalities. In this review, we discuss state-of-the-art ML-based approaches for tackling five specific computational challenges associated with integrative analysis: curse of dimensionality, data heterogeneity, missing data, class imbalance and scalability issues
Ensemble deep learning: A review
Ensemble learning combines several individual models to obtain better
generalization performance. Currently, deep learning models with multilayer
processing architecture is showing better performance as compared to the
shallow or traditional classification models. Deep ensemble learning models
combine the advantages of both the deep learning models as well as the ensemble
learning such that the final model has better generalization performance. This
paper reviews the state-of-art deep ensemble models and hence serves as an
extensive summary for the researchers. The ensemble models are broadly
categorised into ensemble models like bagging, boosting and stacking, negative
correlation based deep ensemble models, explicit/implicit ensembles,
homogeneous /heterogeneous ensemble, decision fusion strategies, unsupervised,
semi-supervised, reinforcement learning and online/incremental, multilabel
based deep ensemble models. Application of deep ensemble models in different
domains is also briefly discussed. Finally, we conclude this paper with some
future recommendations and research directions
Graph based fusion of high-dimensional gene- and microRNA expression data
One of the main goals in cancer studies including high-throughput microRNA
(miRNA) and mRNA data is to find and assess prognostic signatures capable
of predicting clinical outcome. Both mRNA and miRNA expression changes in
cancer diseases are described to reflect clinical characteristics like staging and
prognosis. Furthermore, miRNA abundance can directly affect target transcripts
and translation in tumor cells. Prediction models are trained to identify either
mRNA or miRNA signatures for patient stratification. With the increasing
number of microarray studies collecting mRNA and miRNA from the same
patient cohort there is a need for statistical methods to integrate or fuse both
kinds of data into one prediction model in order to find a combined signature
that improves the prediction.
Here, we propose a new method to fuse miRNA and mRNA data into one
prediction model. Since miRNAs are known regulators of mRNAs, correlations
between miRNA and mRNA expression data as well as target prediction
information were used to build a bipartite graph representing the relations
between miRNAs and mRNAs.
Feature selection is a critical part when fitting prediction models to high-
dimensional data. Most methods treat features, in this case genes or miRNAs,
as independent, an assumption that does not hold true when dealing with
combined gene and miRNA expression data. To improve prediction accuracy, a
description of the correlation structure in the data is needed. In this work the
bipartite graph was used to guide the feature selection and therewith improve
prediction results and find a stable prognostic signature of miRNAs and genes.
The method is evaluated on a prostate cancer data set comprising 98 patient
samples with miRNA and mRNA expression data. The biochemical relapse, an
important event in prostate cancer treatment, was used as clinical endpoint.
Biochemical relapse coins the renewed rise of the blood level of a prostate
marker (PSA) after surgical removal of the prostate. The relapse is a hint
for metastases and usually the point in clinical practise to decide for further
treatment.
A boosting approach was used to predict the biochemical relapse. It could
be shown that the bipartite graph in combination with miRNA and mRNA
expression data could improve prediction performance. Furthermore the ap-
proach improved the stability of the feature selection and therewith yielded
more consistent marker sets. Of course, the marker sets produced by this new
method contain mRNAs as well as miRNAs.
The new approach was compared to two state-of-the-art methods suited for
high-dimensional data and showed better prediction performance in both cases
Artificial Neural Network Inference (ANNI): A Study on Gene-Gene Interaction for Biomarkers in Childhood Sarcomas
Objective: To model the potential interaction between previously identified biomarkers in children sarcomas using artificial neural network inference (ANNI).
Method: To concisely demonstrate the biological interactions between correlated genes in an interaction network map, only 2 types of sarcomas in the children small round blue cell tumors (SRBCTs) dataset are discussed in this paper. A backpropagation neural network was used to model the potential interaction between genes. The prediction weights and signal directions were used to model the strengths of the interaction signals and the direction of the interaction link between genes. The ANN model was validated using Monte Carlo cross-validation to minimize the risk of over-fitting and to optimize generalization ability of the model.
Results: Strong connection links on certain genes (TNNT1 and FNDC5 in rhabdomyosarcoma (RMS); FCGRT and OLFM1 in Ewing’s sarcoma (EWS)) suggested their potency as central hubs in the interconnection of genes with different functionalities. The results showed that the RMS patients in this dataset are likely to be congenital and at low risk of cardiomyopathy development. The EWS patients are likely to be complicated by EWS-FLI fusion and deficiency in various signaling pathways, including Wnt, Fas/Rho and intracellular oxygen.
Conclusions: The ANN network inference approach and the examination of identified genes in the published literature within the context of the disease highlights the substantial influence of certain genes in sarcomas
Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization
Increasing evidence suggests that chromosomal regions containing microRNAs are functionally important in cancers. Here, we show that genomic loci encoding miR-204 are frequently lost in multiple cancers, including ovarian cancers, pediatric renal tumors, and breast cancers. MiR-204 shows drastically reduced expression in several cancers and acts as a potent tumor suppressor, inhibiting tumor metastasis in vivo when systemically delivered. We demonstrated that miR-204 exerts its function by targeting genes involved in tumorigenesis including brain-derived neurotrophic factor (BDNF), a neurotrophin family member which is known to promote tumor angiogenesis and invasiveness. Analysis of primary tumors shows that increased expression of BDNF or its receptor tropomyosin-related kinase B (TrkB) parallel a markedly reduced expression of miR-204. Our results reveal that loss of miR-204 results in BDNF overexpression and subsequent activation of the small GTPase Rac1 and actin reorganization through the AKT/mTOR signaling pathway leading to cancer cell migration and invasion. These results suggest that microdeletion of genomic loci containing miR-204 is directly linked with the deregulation of key oncogenic pathways that provide crucial stimulus for tumor growth and metastasis. Our findings provide a strong rationale for manipulating miR-204 levels therapeutically to suppress tumor metastasis
One-Class Classification: Taxonomy of Study and Review of Techniques
One-class classification (OCC) algorithms aim to build classification models
when the negative class is either absent, poorly sampled or not well defined.
This unique situation constrains the learning of efficient classifiers by
defining class boundary just with the knowledge of positive class. The OCC
problem has been considered and applied under many research themes, such as
outlier/novelty detection and concept learning. In this paper we present a
unified view of the general problem of OCC by presenting a taxonomy of study
for OCC problems, which is based on the availability of training data,
algorithms used and the application domains applied. We further delve into each
of the categories of the proposed taxonomy and present a comprehensive
literature review of the OCC algorithms, techniques and methodologies with a
focus on their significance, limitations and applications. We conclude our
paper by discussing some open research problems in the field of OCC and present
our vision for future research.Comment: 24 pages + 11 pages of references, 8 figure
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