A Novel Approach Searching for Discriminative Gene Sets

Author(s):  
Feng Chu ◽  
Lipo Wang
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Ewoud Ewing ◽  
Nuria Planell-Picola ◽  
Maja Jagodic ◽  
David Gomez-Cabrero

Abstract Background Gene-set analysis tools, which make use of curated sets of molecules grouped based on their shared functions, aim to identify which gene-sets are over-represented in the set of features that have been associated with a given trait of interest. Such tools are frequently used in gene-centric approaches derived from RNA-sequencing or microarrays such as Ingenuity or GSEA, but they have also been adapted for interval-based analysis derived from DNA methylation or ChIP/ATAC-sequencing. Gene-set analysis tools return, as a result, a list of significant gene-sets. However, while these results are useful for the researcher in the identification of major biological insights, they may be complex to interpret because many gene-sets have largely overlapping gene contents. Additionally, in many cases the result of gene-set analysis consists of a large number of gene-sets making it complicated to identify the major biological insights. Results We present GeneSetCluster, a novel approach which allows clustering of identified gene-sets, from one or multiple experiments and/or tools, based on shared genes. GeneSetCluster calculates a distance score based on overlapping gene content, which is then used to cluster them together and as a result, GeneSetCluster identifies groups of gene-sets with similar gene-set definitions (i.e. gene content). These groups of gene-sets can aid the researcher to focus on such groups for biological interpretations. Conclusions GeneSetCluster is a novel approach for grouping together post gene-set analysis results based on overlapping gene content. GeneSetCluster is implemented as a package in R. The package and the vignette can be downloaded at https://github.com/TranslationalBioinformaticsUnit


2018 ◽  
Author(s):  
Hong-Dong Li ◽  
Yunpei Xu ◽  
Xiaoshu Zhu ◽  
Quan Liu ◽  
Gilbert S. Omenn ◽  
...  

ABSTRACTMotivationClustering analysis is essential for understanding complex biological data. In widely used methods such as hierarchical clustering (HC) and consensus clustering (CC), expression profiles of all genes are often used to assess similarity between samples for clustering. These methods output sample clusters, but are not able to provide information about which gene sets (functions) contribute most to the clustering. So interpretability of their results is limited. We hypothesized that integrating prior knowledge of annotated biological processes would not only achieve satisfying clustering performance but also, more importantly, enable potential biological interpretation of clusters.ResultsHere we report ClusterMine, a novel approach that identifies clusters by assessing functional similarity between samples through integrating known annotated gene sets, e.g., in Gene Ontology. In addition to outputting cluster membership of each sample as conventional approaches do, it outputs gene sets that are most likely to contribute to the clustering, a feature facilitating biological interpretation. Using three cancer datasets, two single cell RNA-sequencing based cell differentiation datasets, one cell cycle dataset and two datasets of cells of different tissue origins, we found that ClusterMine achieved similar or better clustering performance and that top-scored gene sets prioritized by ClusterMine are biologically relevant.Implementation and availabilityClusterMine is implemented as an R package and is freely available at: www.genemine.org/[email protected] InformationSupplementary data are available at Bioinformatics online.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hong-Li Hua ◽  
Fa-Zhan Zhang ◽  
Abraham Alemayehu Labena ◽  
Chuan Dong ◽  
Yan-Ting Jin ◽  
...  

Investigation of essential genes is significant to comprehend the minimal gene sets of cell and discover potential drug targets. In this study, a novel approach based on multiple homology mapping and machine learning method was introduced to predict essential genes. We focused on 25 bacteria which have characterized essential genes. The predictions yielded the highest area under receiver operating characteristic (ROC) curve (AUC) of 0.9716 through tenfold cross-validation test. Proper features were utilized to construct models to make predictions in distantly related bacteria. The accuracy of predictions was evaluated via the consistency of predictions and known essential genes of target species. The highest AUC of 0.9552 and average AUC of 0.8314 were achieved when making predictions across organisms. An independent dataset fromSynechococcus elongatus, which was released recently, was obtained for further assessment of the performance of our model. The AUC score of predictions is 0.7855, which is higher than other methods. This research presents that features obtained by homology mapping uniquely can achieve quite great or even better results than those integrated features. Meanwhile, the work indicates that machine learning-based method can assign more efficient weight coefficients than using empirical formula based on biological knowledge.


2020 ◽  
Vol 48 (17) ◽  
pp. e98-e98
Author(s):  
Gal Barel ◽  
Ralf Herwig

Abstract We present NetCore, a novel network propagation approach based on node coreness, for phenotype–genotype associations and module identification. NetCore addresses the node degree bias in PPI networks by using node coreness in the random walk with restart procedure, and achieves improved re-ranking of genes after propagation. Furthermore, NetCore implements a semi-supervised approach to identify phenotype-associated network modules, which anchors the identification of novel candidate genes at known genes associated with the phenotype. We evaluated NetCore on gene sets from 11 different GWAS traits and showed improved performance compared to the standard degree-based network propagation using cross-validation. Furthermore, we applied NetCore to identify disease genes and modules for Schizophrenia GWAS data and pan-cancer mutation data. We compared the novel approach to existing network propagation approaches and showed the benefits of using NetCore in comparison to those. We provide an easy-to-use implementation, together with a high confidence PPI network extracted from ConsensusPathDB, which can be applied to various types of genomics data in order to obtain a re-ranking of genes and functionally relevant network modules.


2019 ◽  
Vol 476 (24) ◽  
pp. 3705-3719 ◽  
Author(s):  
Avani Vyas ◽  
Umamaheswar Duvvuri ◽  
Kirill Kiselyov

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.


2020 ◽  
Vol 51 (3) ◽  
pp. 544-560 ◽  
Author(s):  
Kimberly A. Murphy ◽  
Emily A. Diehm

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687


2015 ◽  
Vol 21 ◽  
pp. 128
Author(s):  
Kaniksha Desai ◽  
Halis Akturk ◽  
Ana Maria Chindris ◽  
Shon Meek ◽  
Robert Smallridge ◽  
...  
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