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      Identifying Discriminative Biological Function Features and Rules for Cancer-Related Long Non-coding RNAs

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          Abstract

          Cancer has been a major public health problem worldwide for many centuries. Cancer is a complex disease associated with accumulative genetic mutations, epigenetic aberrations, chromosomal instability, and expression alteration. Increasing lines of evidence suggest that many non-coding transcripts, which are termed as non-coding RNAs, have important regulatory roles in cancer. In particular, long non-coding RNAs (lncRNAs) play crucial roles in tumorigenesis. Cancer-related lncRNAs serve as oncogenic factors or tumor suppressors. Although many lncRNAs are identified as potential regulators in tumorigenesis by using traditional experimental methods, they are time consuming and expensive considering the tremendous amount of lncRNAs needed. Thus, effective and fast approaches to recognize tumor-related lncRNAs should be developed. The proposed approach should help us understand not only the mechanisms of lncRNAs that participate in tumorigenesis but also their satisfactory performance in distinguishing cancer-related lncRNAs. In this study, we utilized a decision tree (DT), a type of rule learning algorithm, to investigate cancer-related lncRNAs with functional annotation contents [gene ontology (GO) terms and KEGG pathways] of their co-expressed genes. Cancer-related and other lncRNAs encoded by the key enrichment features of GO and KEGG filtered by feature selection methods were used to build an informative DT, which further induced several decision rules. The rules provided not only a new tool for identifying cancer-related lncRNAs but also connected the lncRNAs and cancers with the combinations of GO terms. Results provided new directions for understanding cancer-related lncRNAs.

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          Most cited references72

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          SMOTE: Synthetic Minority Over-sampling Technique

          An approach to the construction of classifiers from imbalanced datasets is described. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ``normal'' examples with only a small percentage of ``abnormal'' or ``interesting'' examples. It is also the case that the cost of misclassifying an abnormal (interesting) example as a normal example is often much higher than the cost of the reverse error. Under-sampling of the majority (normal) class has been proposed as a good means of increasing the sensitivity of a classifier to the minority class. This paper shows that a combination of our method of over-sampling the minority (abnormal) class and under-sampling the majority (normal) class can achieve better classifier performance (in ROC space) than only under-sampling the majority class. This paper also shows that a combination of our method of over-sampling the minority class and under-sampling the majority class can achieve better classifier performance (in ROC space) than varying the loss ratios in Ripper or class priors in Naive Bayes. Our method of over-sampling the minority class involves creating synthetic minority class examples. Experiments are performed using C4.5, Ripper and a Naive Bayes classifier. The method is evaluated using the area under the Receiver Operating Characteristic curve (AUC) and the ROC convex hull strategy.
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            Cancer statistics, 2016.

            Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute (Surveillance, Epidemiology, and End Results [SEER] Program), the Centers for Disease Control and Prevention (National Program of Cancer Registries), and the North American Association of Central Cancer Registries. Mortality data were collected by the National Center for Health Statistics. In 2016, 1,685,210 new cancer cases and 595,690 cancer deaths are projected to occur in the United States. Overall cancer incidence trends (13 oldest SEER registries) are stable in women, but declining by 3.1% per year in men (from 2009-2012), much of which is because of recent rapid declines in prostate cancer diagnoses. The cancer death rate has dropped by 23% since 1991, translating to more than 1.7 million deaths averted through 2012. Despite this progress, death rates are increasing for cancers of the liver, pancreas, and uterine corpus, and cancer is now the leading cause of death in 21 states, primarily due to exceptionally large reductions in death from heart disease. Among children and adolescents (aged birth-19 years), brain cancer has surpassed leukemia as the leading cause of cancer death because of the dramatic therapeutic advances against leukemia. Accelerating progress against cancer requires both increased national investment in cancer research and the application of existing cancer control knowledge across all segments of the population.
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              RNA maps reveal new RNA classes and a possible function for pervasive transcription.

              Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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                Author and article information

                Contributors
                Journal
                Front Genet
                Front Genet
                Front. Genet.
                Frontiers in Genetics
                Frontiers Media S.A.
                1664-8021
                16 December 2020
                2020
                : 11
                : 598773
                Affiliations
                [1] 1School of Life Sciences, Shanghai University , Shanghai, China
                [2] 2Department of Medical Oncology, Shanghai Concord Medical Cancer Center , Shanghai, China
                Author notes

                Edited by: Jialiang Yang, Genesis Beijing Co., Ltd., China

                Reviewed by: Ju Xiang, Changsha Medical University, China; Lihong Peng, Hunan University of Technology, China

                *Correspondence: Liucun Zhu, zhuliucun@ 123456shu.edu.cn

                This article was submitted to Computational Genomics, a section of the journal Frontiers in Genetics

                Article
                10.3389/fgene.2020.598773
                7772407
                33391350
                7ed39748-9219-47f3-8e08-c4d4a999190a
                Copyright © 2020 Zhu, Yang, Zhu and Yu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 August 2020
                : 23 November 2020
                Page count
                Figures: 4, Tables: 1, Equations: 5, References: 72, Pages: 9, Words: 0
                Categories
                Genetics
                Original Research

                Genetics
                decision rule,kegg pathway,gene ontology,decision tree,long non-coding rnas,cancer
                Genetics
                decision rule, kegg pathway, gene ontology, decision tree, long non-coding rnas, cancer

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