Journal ArticleDOI

# An Integrated Approach for Identification of Functionally Similar MicroRNAs in Colorectal Cancer

01 Jan 2019--Vol. 16, Iss: 1, pp 183-192

TL;DR: A new algorithm, called Sim, is presented, an integrative approach for identification of functionally similar miRNAs associated with CRC that integrates judiciously the information of miRNA expression data and miRNA-miRNA functionally synergistic network data.

AbstractColorectal cancer (CRC) is one of the most prevalent cancers around the globe. However, the molecular reasons for pathogenesis of CRC are still poorly understood. Recently, the role of microRNAs or miRNAs in the initiation and progression of CRC has been studied. MicroRNAs are small, endogenous noncoding RNAs found in plants, animals, and some viruses, which function in RNA silencing and posttranscriptional regulation of gene expression. Their role in CRC development is studied and they are found to be potential biomarkers in diagnosis and treatment of CRC. Therefore, identification of functionally similar CRC related miRNAs may help in the development of a prognostic tool. In this regard, this paper presents a new algorithm, called $\mu$ Sim. It is an integrative approach for identification of functionally similar miRNAs associated with CRC. It integrates judiciously the information of miRNA expression data and miRNA-miRNA functionally synergistic network data. The functional similarity is calculated based on both miRNA expression data and miRNA-miRNA functionally synergistic network data. The effectiveness of the proposed method in comparison to other related methods is shown on four CRC miRNA data sets. The proposed method selected more significant miRNAs related to CRC as compared to other related methods.

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TL;DR: A novel strategy for the cox model is suggested that combines a new learning technique, self-paced learning (SPL), and a new gene selection method, SCAD-Net penalty, to build a more accurate prediction with its built-in mechanism of learning from easy samples first and adaptively learning from hard samples.
Abstract: The Cox proportional hazards model is a popular method to study the connection between feature and survival time. Because of the high-dimensionality of genomic data, existing Cox models trained on any specific dataset often generalize poorly to other independent datasets. In this paper, we suggest a novel strategy for the Cox model. This strategy is included a new learning technique, self-paced learning (SPL), and a new gene selection method, SCAD-Net penalty. The SPL method is adopted to aid to build a more accurate prediction with its built-in mechanism of learning from easy samples first and adaptively learning from hard samples. The SCAD-Net penalty has fixed the problem of the SCAD method without an inherent mechanism to fuse the prior graphical information. We combined the SPL with the SCAD-Net penalty to the Cox model (SSNC). The simulation shows that the SSNC outperforms the benchmark in terms of prediction and gene selection. The analysis of a large-scale experiment across several cancer datasets shows that the SSNC method not only results in higher prediction accuracies but also identifies markers that satisfactory stability across another validation dataset. The demo code for the proposed method is provided in supplemental file.

2 citations

Journal ArticleDOI
04 Oct 2021-Viruses
TL;DR: In this paper, the authors discuss how miRNAs could relate to ZIKV and other flavivirus infections, and discuss the role of microRNAs in the pathogenesis of viral infections.
Abstract: Over the years, viral infections have caused severe illness in humans. Zika Virus (ZIKV) is a flavivirus transmitted by mosquito vectors that leads to notable neurological impairment, whose most dramatic impact is the Congenital ZIKV Syndrome (CZS). ZIKV targets neuronal precursor cells leading to apoptosis and further impairment of neuronal development, causing microcephaly, lissencephaly, ventriculomegaly, and calcifications. Several regulators of biological processes are involved in CZS development, and in this context, microRNAs (miRNAs) seem to have a fundamental role. miRNAs are important regulators of protein translation, as they form the RISC silencing complex and interact with complementary mRNA target sequences to further post-transcriptional repression. In this context, little is known about their participation in the pathogenesis of viral infections. In this review, we discuss how miRNAs could relate to ZIKV and other flavivirus infections.

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Journal ArticleDOI
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TL;DR: Internal estimates monitor error, strength, and correlation and these are used to show the response to increasing the number of features used in the forest, and are also applicable to regression.
Abstract: Random forests are a combination of tree predictors such that each tree depends on the values of a random vector sampled independently and with the same distribution for all trees in the forest. The generalization error for forests converges a.s. to a limit as the number of trees in the forest becomes large. The generalization error of a forest of tree classifiers depends on the strength of the individual trees in the forest and the correlation between them. Using a random selection of features to split each node yields error rates that compare favorably to Adaboost (Y. Freund & R. Schapire, Machine Learning: Proceedings of the Thirteenth International conference, aaa, 148–156), but are more robust with respect to noise. Internal estimates monitor error, strength, and correlation and these are used to show the response to increasing the number of features used in the splitting. Internal estimates are also used to measure variable importance. These ideas are also applicable to regression.

58,232 citations

### "An Integrated Approach for Identifi..." refers background or methods in this paper

• ...The performance of the proposed miRNA selection (mSim) method is extensively studied and compared with that of some existing algorithms, namely, CFS [19], Ebayes [17], PLSCV [19], RFMDA [20], SAM [18], CLAIM [28], and RelSim [27]....

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• ...miRNAs frommicroarray miRNA expression data [17], [18], [19], [20], [21], [22]....

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Journal ArticleDOI

TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Abstract: The global burden of cancer continues to increase largely because of the aging and growth of the world population alongside an increasing adoption of cancer-causing behaviors, particularly smoking, in economically developing countries. Based on the GLOBOCAN 2008 estimates, about 12.7 million cancer cases and 7.6 million cancer deaths are estimated to have occurred in 2008; of these, 56% of the cases and 64% of the deaths occurred in the economically developing world. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% of the total cancer cases and 14% of the cancer deaths. Lung cancer is the leading cancer site in males, comprising 17% of the total new cancer cases and 23% of the total cancer deaths. Breast cancer is now also the leading cause of cancer death among females in economically developing countries, a shift from the previous decade during which the most common cause of cancer death was cervical cancer. Further, the mortality burden for lung cancer among females in developing countries is as high as the burden for cervical cancer, with each accounting for 11% of the total female cancer deaths. Although overall cancer incidence rates in the developing world are half those seen in the developed world in both sexes, the overall cancer mortality rates are generally similar. Cancer survival tends to be poorer in developing countries, most likely because of a combination of a late stage at diagnosis and limited access to timely and standard treatment. A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination (for liver and cervical cancers), and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake. Clinicians, public health professionals, and policy makers can play an active role in accelerating the application of such interventions globally.

51,138 citations

### "An Integrated Approach for Identifi..." refers background in this paper

• ...1 per 100,000 men and women per year [1]....

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Journal ArticleDOI
TL;DR: A method that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements is described, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.
Abstract: Microarrays can measure the expression of thousands of genes to identify changes in expression between different biological states. Methods are needed to determine the significance of these changes while accounting for the enormous number of genes. We describe a method, Significance Analysis of Microarrays (SAM), that assigns a score to each gene on the basis of change in gene expression relative to the standard deviation of repeated measurements. For genes with scores greater than an adjustable threshold, SAM uses permutations of the repeated measurements to estimate the percentage of genes identified by chance, the false discovery rate (FDR). When the transcriptional response of human cells to ionizing radiation was measured by microarrays, SAM identified 34 genes that changed at least 1.5-fold with an estimated FDR of 12%, compared with FDRs of 60 and 84% by using conventional methods of analysis. Of the 34 genes, 19 were involved in cell cycle regulation and 3 in apoptosis. Surprisingly, four nucleotide excision repair genes were induced, suggesting that this repair pathway for UV-damaged DNA might play a previously unrecognized role in repairing DNA damaged by ionizing radiation.

11,833 citations

### "An Integrated Approach for Identifi..." refers background or methods in this paper

• ...The performance of the proposed miRNA selection (mSim) method is extensively studied and compared with that of some existing algorithms, namely, CFS [19], Ebayes [17], PLSCV [19], RFMDA [20], SAM [18], CLAIM [28], and RelSim [27]....

[...]

• ...The luciferase activity assay and western blot study in this TABLE 4 Significant Shared Pathway Term (Colorectal Cancer) for miRNAs Obtained by Different Methods Algorithm Methods GSE35602 GSE48267 GSE54632 GSE57969 P -value Genes miRNAs P -value Genes miRNAs P -value Genes miRNAs P -value Genes miRNAs CFS 4.90E-05 1 1 4.65E-07 3 2 2.33E-15 16 3 - - - Ebayes 0.00E+00 10 5 0.00E+00 13 5 0.00E+00 19 5 6.73E-08 6 1 PLS 0.00E+00 10 6 7.72E-09 4 2 0.00E+00 20 7 - - - RF-MDA 9.03E-14 8 4 0.00E+00 13 6 0.00E+00 17 5 1.42E-03 2 1 SAM 0.00E+00 10 5 1.11E-16 12 5 0.00E+00 19 6 - - - Info Gain 6.21E-06 4 2 0.00E+00 10 5 - - - - - - Vnet - - - 0.00E+00 18 6 - - - - - - Vexp - - - 1.11E-16 10 4 - - - - - - CLAIM 8.18E-12 6 5 0.00E+00 8 4 0.00E+00 8 5 2.32E-07 4 2 RelSim 0.00E+00 10 5 0.00E+00 12 7 - - - 2.52E-09 6 2 mSim 0.00E+00 17 5 0.00E+00 19 8 - - - 1.11E-15 6 3 paper show that the cholecystokinin-2 receptor gene (CCK2R) is a target of hsa-miR-148b-3p and gets downregulated by hsa-miR-148b-3p at the translational level....

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• ...miRNAs frommicroarray miRNA expression data [17], [18], [19], [20], [21], [22]....

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• ...TABLE 1 Comparative Performance of Different miRNA Selection Algorithms Algorithms Methods GSE35602 GSE48267 GSE54632 GSE57969 miRNAs P -value miRNAs P -value miRNAs P -value miRNAs P -value CFS 6 2.26E-02 9 2.26E-02 19 1.23E-03 6 4.50E-01 Ebayes 19 2.26E-02 21 1.14E-04 23 6.54E-06 14 9.76E-02 PLS 22 2.58E-05 16 2.45E-02 25 3.26E-07 14 9.76E-02 RF-MDA 21 1.14E-04 24 1.52E-06 23 6.54E-06 14 9.76E-02 SAM 19 1.23E-03 19 1.23E-03 23 6.54E-06 12 3.55E-01 Info Gain 19 1.23E-03 20 3.34E-04 15 6.14E-02 8 7.12E-01 Vnet 13 1.96E-01 28 1.93E-09 4 4.17E-02 17 8.83E-03 Vexp 28 1.93E-09 18 4.51E-03 8 7.12E-01 21 1.14E-04 mSim 34 6.42E-15 33 6.60E-14 25 3.26E-07 20 3.34E-04...

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Journal ArticleDOI
TL;DR: It is shown here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity and established the measurement of tumor-derived mi RNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
Abstract: Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small (≈22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.

6,658 citations

### "An Integrated Approach for Identifi..." refers background in this paper

• ...Their roles have been studied in many crucial biological processes, including development, differentiation, apoptosis and cell proliferation [4], [5], [6], [7], as well as numerous human diseases, such as chronic lymphocytic leukemia, fragile X syndrome, and various types of cancers [8], [9], [10], [11], [12]....

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Journal ArticleDOI
TL;DR: Two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events and indicate the existence of multiple RISCs that carry out related but specific biological functions.
Abstract: MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. The two founding members of the microRNA family were originally identified in Caenorhabditis elegans as genes that were required for the timed regulation of developmental events. Since then, hundreds of microRNAs have been identified in almost all metazoan genomes, including worms, flies, plants and mammals. MicroRNAs have diverse expression patterns and might regulate various developmental and physiological processes. Their discovery adds a new dimension to our understanding of complex gene regulatory networks.

5,862 citations

### "An Integrated Approach for Identifi..." refers background in this paper

• ...Their roles have been studied in many crucial biological processes, including development, differentiation, apoptosis and cell proliferation [4], [5], [6], [7], as well as numerous human diseases, such as chronic lymphocytic leukemia, fragile X syndrome, and various types of cancers [8], [9], [10], [11], [12]....

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