{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T06:51:19Z","timestamp":1782629479994,"version":"3.54.5"},"reference-count":69,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Horizon 2020 Research and Innovation Framework Programme","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"Horizon 2020 Research and Innovation Framework Programme","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"ERA-NET PerMed","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"ERA-NET PerMed","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"The Edmond J. Safra Center for Bioinformatics at Tel Aviv University","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"The Edmond J. Safra Center for Bioinformatics at Tel Aviv University","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"The Koret-UC Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"The Koret-UC Berkeley-Tel Aviv University Initiative in Computational Biology and Bioinformatics","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"Djerassi-Elias Institute of Oncology","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"Djerassi-Elias Institute of Oncology","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"Kirschman Dvora Eleonora Fund for Parkinson\u2019s Disease","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"Kirschman Dvora Eleonora Fund for Parkinson\u2019s Disease","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"Tel Aviv University Innovation Laboratories (TILabs), Israeli Innovative Authority (Liquid Biospy, BX)","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"Tel Aviv University Innovation Laboratories (TILabs), Israeli Innovative Authority (Liquid Biospy, BX)","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]},{"name":"Halperin-Bernstein Esther support for Cancer Research","award":["945151"],"award-info":[{"award-number":["945151"]}]},{"name":"Halperin-Bernstein Esther support for Cancer Research","award":["3-17928"],"award-info":[{"award-number":["3-17928"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most lethal cancers, accounting for a significant proportion of cancer-related deaths globally. Despite advancements in medical science, treatment options for PDAC remain limited, and the prognosis is often poor. Early detection is a critical factor in improving patient outcomes, but current diagnostic methods often fail to detect PDAC until it has advanced to a late stage. In this context, the development of more effective diagnostic tools is of paramount importance. In this study, we explored the potential of non-coding RNAs (ncRNAs) as diagnostic markers for PDAC using cell-free nucleotides and liquid biopsies. Leveraging the power of Next Generation Sequencing (NGS), bioinformatics analysis, and machine learning (ML), we were able to identify unique RNA signatures associated with PDAC. Our findings revealed twenty key genes, including microRNAs (miRNAs), long-non-coding RNAs (lncRNAs), and miscellaneous RNAs that demonstrated high classification accuracy. Specifically, our model achieved a classification accuracy of 87% and an area under the receiver operating characteristic curve (AUC) of 91%. These ncRNAs could potentially serve as robust biomarkers for PDAC, offering a promising avenue for the development of a non-invasive diagnostic test. This could revolutionize PDAC diagnosis, enabling earlier detection and intervention, which is crucial for improving patient outcomes. This work lays the groundwork for future research, with the potential to significantly enhance PDAC diagnosis and therapy.<\/jats:p>","DOI":"10.3390\/ijms26168108","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T07:41:45Z","timestamp":1755848505000},"page":"8108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Deciphering the Diagnostic Potential of Small Non-Coding RNAs for the Detection of Pancreatic Ductal Adenocarcinoma Through Liquid Biopsies"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1749-405X","authenticated-orcid":false,"given":"Hadas","family":"Volkov","sequence":"first","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rani","family":"Shlayem","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9913-6124","authenticated-orcid":false,"given":"Noam","family":"Shomron","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 69978, Israel"},{"name":"Edmond J. Safra Center for Bioinformatics, Tel Aviv University, Tel Aviv 69978, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"ref_1","first-page":"271","article-title":"Cancer treatment and survivorship statistics, 2016","volume":"66","author":"Miller","year":"2016","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Sally, \u00c1., McGowan, R., Finn, K., and Moran, B.M. (2022). Current and Future Therapies for Pancreatic Ductal Adenocarcinoma. Cancers, 14.","DOI":"10.3390\/cancers14102417"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s13014-019-1345-6","article-title":"Pancreatic ductal adenocarcinoma: Biological hallmarks, current status, and future perspectives of combined modality treatment approaches","volume":"14","author":"Orth","year":"2019","journal-title":"Radiat. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Amrutkar, M., and Gladhaug, I.P. (2017). Pancreatic Cancer Chemoresistance to Gemcitabine. Cancers, 9.","DOI":"10.3390\/cancers9110157"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"216636","DOI":"10.1016\/j.canlet.2024.216636","article-title":"Precision treatment of pancreatic ductal adenocarcinoma","volume":"585","author":"Wei","year":"2024","journal-title":"Cancer Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1038\/s41571-020-0363-5","article-title":"The tumour microenvironment in pancreatic cancer\u2014Clinical challenges and opportunities","volume":"17","author":"Ho","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2269","DOI":"10.1038\/bjc.2014.123","article-title":"Ascites-derived pancreatic ductal adenocarcinoma primary cell cultures as a platform for personalised medicine","volume":"110","author":"Golan","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Nakaoka, K., Ohno, E., Kawabe, N., Kuzuya, T., Funasaka, K., Nakagawa, Y., Nagasaka, M., Ishikawa, T., Watanabe, A., and Tochio, T. (2023). Current Status of the Diagnosis of Early-Stage Pancreatic Ductal Adenocarcinoma. Diagnostics, 13.","DOI":"10.3390\/diagnostics13020215"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.ijscr.2018.11.022","article-title":"Dilemmas and limitations interpreting carbohydrate antigen 19-9 elevation after curative pancreatic surgery: A case report","volume":"54","author":"Gold","year":"2018","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Azizian, A., R\u00fchlmann, F., Krause, T., Bernhardt, M., Jo, P., K\u00f6nig, A., Klei\u00df, M., Leha, A., Ghadimi, M., and Gaedcke, J. (2020). CA19-9 for detecting recurrence of pancreatic cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-57930-x"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ramanathan, L.V., Fleisher, M., and Duffy, M.J. (2022). Chapter 1-Overview of traditional and nontraditional tumor markers. Cancer Biomarkers, Elsevier. Clinical Aspects and Laboratory Determination.","DOI":"10.1016\/B978-0-12-824302-2.00004-7"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"101730","DOI":"10.1016\/j.tranon.2023.101730","article-title":"Unlocking the potential of non-coding RNAs in cancer research and therapy","volume":"35","author":"Uppaluri","year":"2023","journal-title":"Transl. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1038\/s41551-023-01081-7","article-title":"Profiling of repetitive RNA sequences in the blood plasma of patients with cancer","volume":"7","author":"Reggiardo","year":"2023","journal-title":"Nat. Biomed. Eng."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Qian, Y., Shi, L., and Luo, Z. (2020). Long Non-coding RNAs in Cancer: Implications for Diagnosis, Prognosis, and Therapy. Front. Med., 7.","DOI":"10.3389\/fmed.2020.612393"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Karimzadeh, M., Wang, J., Cavazos, T.B., Schwartzberg, L.S., Multhaup, M., Ku, J., Zhao, X., Wang, J., Wang, K., and Hanna, R. (2023). Detection of early-stage cancers using circulating orphan non-coding RNAs in blood. J. Clin. Oncol., 41.","DOI":"10.1200\/JCO.2023.41.16_suppl.3051"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/s41392-022-00975-3","article-title":"Targeting non-coding RNAs to overcome cancer therapy resistance","volume":"7","author":"Chen","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gul\u00eca, C., Signore, F., Gaffi, M., Gigli, S., Votino, R., Nucciotti, R., Bertacca, L., Zaami, S., Baffa, A., and Santini, E. (2020). Y RNA: An Overview of Their Role as Potential Biomarkers and Molecular Targets in Human Cancers. Cancers, 12.","DOI":"10.3390\/cancers12051238"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"100581","DOI":"10.1016\/j.imu.2021.100581","article-title":"Newaz Mohammed Bahadur c, Md Mizanur Rahaman d. Prediction of novel miRNA biomarker candidates for diagnostic and prognostic analysis of STAD and LIHC: An integrated in silico approach","volume":"24","author":"Kar","year":"2021","journal-title":"Inform. Med. Unlocked."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/s41417-024-00741-3","article-title":"Utilizing nullomers in cell-free RNA for early cancer detection","volume":"31","author":"Montgomery","year":"2024","journal-title":"Cancer Gene Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Moro, L. (2021). Mitochondrial DNA and MitomiR Variations in Pancreatic Cancer: Potential Diagnostic and Prognostic Biomarkers. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22189692"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"12868","DOI":"10.1038\/ncomms12868","article-title":"Local microRNA delivery targets Palladin and prevents metastatic breast cancer","volume":"7","author":"Gilam","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e00029","DOI":"10.14309\/ctg.0000000000000029","article-title":"Novel Circulating miRNA Signatures for Early Detection of Pancreatic Neoplasia","volume":"10","author":"Moreira","year":"2019","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Aita, A., Millino, C., Sperti, C., Pacchioni, B., Plebani, M., De Pitt\u00e0, C., and Basso, D. (2021). Serum miRNA Profiling for Early PDAC Diagnosis and Prognosis: A Retrospective Study. Biomedicines, 9.","DOI":"10.3390\/biomedicines9070845"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nishibeppu, K., Komatsu, S., Imamura, T., Kiuchi, J., Kishimoto, T., Arita, T., Kosuga, T., Konishi, H., Kubota, T., and Shiozaki, A. (2020). Plasma microRNA profiles: Identification of miR-1229-3p as a novel chemoresistant and prognostic biomarker in gastric cancer. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-59939-8"},{"key":"ref_25","unstructured":"(2024, August 02). miRNA and Gene Expression in Pancreatic Ductal Adenocarcinoma-PMC, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6854437\/."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Yang, S., Ji, J., Wang, M., Nie, J., and Wang, S. (2023). Construction of Ovarian Cancer Prognostic Model Based on the Investigation of Ferroptosis-Related lncRNA. Biomolecules, 13.","DOI":"10.3390\/biom13020306"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1053\/j.gastro.2023.09.050","article-title":"A circulating panel of circRNA biomarkers for the noninvasive and early detection of pancreatic ductal adenocarcinoma","volume":"166","author":"Xu","year":"2023","journal-title":"Gastroenterology"},{"key":"ref_28","unstructured":"(2024, August 30). Overview of Cellular Senescence and Aging. Cell Signaling Technology. Available online: https:\/\/www.cellsignal.com\/science-resources\/overview-of-cellular-senescence."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xu, J., Hu, S., Chen, Q., Shu, L., Wang, P., and Wang, J. (2023). Integrated bioinformatics analysis of noncoding RNAs with tumor immune microenvironment in gastric cancer. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-41444-3"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.omtn.2019.01.009","article-title":"miR-223 Regulates Cell Proliferation and Invasion via Targeting PDS5B in Pancreatic Cancer Cells","volume":"14","author":"Ma","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Aziz, F., Chakraborty, A., Khan, I., and Monts, J. (2022). Relevance of miR-223 as Potential Diagnostic and Prognostic Markers in Cancer. Biology, 11.","DOI":"10.3390\/biology11020249"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.1007\/s13277-014-2907-8","article-title":"7SK small nuclear RNA inhibits cancer cell proliferation through apoptosis induction","volume":"36","author":"Keramati","year":"2015","journal-title":"Tumor Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.18632\/oncotarget.26804","article-title":"MicroRNA profiling of pancreatic ductal adenocarcinoma (PDAC) reveals signature expression related to lymph node metastasis","volume":"10","author":"Lemberger","year":"2019","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Girolimetti, G., Pelisenco, I.A., Eusebi, L.H., Ricci, C., Cavina, B., Kurelac, I., Verri, T., Calcagnile, M., Alifano, P., and Salvi, A. (2024). Dysregulation of a Subset of Circulating and Vesicle-Associated miRNA in Pancreatic Cancer. Non-Coding RNA, 10.","DOI":"10.3390\/ncrna10030029"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Dhayat, S.A., Mardin, W.A., Seggewi\u00df, J., Str\u00f6se, A.J., Matuszcak, C., Hummel, R., Senninger, N., Mees, S.Y., and Haier, J. (2015). MicroRNA Profiling Implies New Markers of Gemcitabine Chemoresistance in Mutant p53 Pancreatic Ductal Adenocarcinoma. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143755"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"O\u2019Neill, F., Allen-Coyle, T.J., Roche, S., Meiller, J., Conlon, N.T., Swan, N., Straubinger, R.M., Geoghegan, J., Straubinger, N.L., and Conlon, K. (2023). Alteration in Levels of Specific miRNAs and Their Potential Protein Targets between Human Pancreatic Cancer Samples, Adjacent Normal Tissue, and Xenografts Derived from These Tumors. Life, 13.","DOI":"10.3390\/life13030608"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D222","DOI":"10.1093\/nar\/gkab1079","article-title":"miRTarBase update 2022: An informative resource for experimentally validated miRNA\u2013target interactions","volume":"50","author":"Huang","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.2147\/OTT.S232464","article-title":"Is there a CDKN2A-centric network in pancreatic ductal adenocarcinoma?","volume":"13","author":"Wu","year":"2020","journal-title":"OncoTargets Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1128\/MCB.02147-06","article-title":"E2f1, E2f2, and E2f3 Control E2F Target Expression and Cellular Proliferation via a p53-Dependent Negative Feedback Loop","volume":"27","author":"Timmers","year":"2007","journal-title":"Mol. Cell. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Liu, Y., Wang, D., Li, Z., Li, X., Jin, M., Jia, N., Cui, X., Hu, G., Tang, T., and Yu, Q. (2022). Pan-cancer analysis on the role of PIK3R1 and PIK3R2 in human tumors. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-09889-0"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.4161\/auto.29639","article-title":"BCL2 and related prosurvival proteins require BAK1 and BAX to affect autophagy","volume":"10","author":"Lindqvist","year":"2014","journal-title":"Autophagy"},{"key":"ref_42","first-page":"209","article-title":"RAD51 as a potential biomarker and therapeutic target for pancreatic cancer","volume":"1816","author":"Nagathihalli","year":"2011","journal-title":"Biochim. Biophys. Acta BBA-Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"173","DOI":"10.4251\/wjgo.v12.i2.173","article-title":"Pancreatic ductal adenocarcinoma: Treatment hurdles, tumor microenvironment and immunotherapy","volume":"12","author":"Sarantis","year":"2020","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12957-023-03141-3","article-title":"Risk factors for early recurrence in patients with pancreatic ductal adenocarcinoma who underwent curative resection","volume":"21","author":"Murakawa","year":"2023","journal-title":"World J. Surg. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1186\/s12943-018-0897-7","article-title":"Effect of exosomal miRNA on cancer biology and clinical applications","volume":"17","author":"Sun","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.biocel.2015.07.003","article-title":"Functional roles of non-coding Y RNAs","volume":"66","author":"Kowalski","year":"2015","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2772","DOI":"10.1007\/s12094-023-03149-x","article-title":"Deleted in lymphocytic leukemia 2 (DLEU2): A possible biomarker that holds promise for future diagnosis and treatment of cancer","volume":"25","author":"Qu","year":"2023","journal-title":"Clin. Transl. Oncol."},{"key":"ref_48","first-page":"5892","article-title":"RP11-874J12.4, a novel lncRNA, confers chemoresistance in human gastric cancer cells by sponging miR-3972 and upregulating SSR2 expression","volume":"13","author":"Liu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_49","unstructured":"(2024, September 01). QIAamp Circulating Nucleic Acid Kit | ccfDNA\/RNA | QIAGEN. Available online: https:\/\/www.qiagen.com\/us\/products\/discovery-and-translational-research\/dna-rna-purification\/dna-purification\/cell-free-dna\/qiaamp-circulating-nucleic-acid-kit."},{"key":"ref_50","unstructured":"(2024, September 10). QubitTM RNA High Sensitivity (HS), Broad Range (BR), and Extended Range (XR) Assay Kits. Available online: https:\/\/www.thermofisher.com\/order\/catalog\/product\/Q32855."},{"key":"ref_51","unstructured":"(2024, September 10). Small RNA Electrophoresis, MicroRNA, Bioanalyzer Small RNA | Agilent. Available online: https:\/\/www.agilent.com\/en\/product\/automated-electrophoresis\/bioanalyzer-systems\/bioanalyzer-rna-kits-reagents\/bioanalyzer-small-rna-analysis-228257."},{"key":"ref_52","unstructured":"(2024, September 01). SMARTer smRNA-Seq Kit for Illumina\u2014Sequence Small RNAs with High Sensitivity and Minimal Bias. Available online: https:\/\/www.takarabio.com\/products\/next-generation-sequencing\/rna-seq\/small-rna-seq."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e107","DOI":"10.1002\/imt2.107","article-title":"Ultrafast one-pass FASTQ data preprocessing, quality control, and deduplication using fastp","volume":"2","author":"Chen","year":"2023","journal-title":"iMeta"},{"key":"ref_54","unstructured":"(2024, August 29). Babraham Bioinformatics-FastQC A Quality Control Tool for High Throughput Sequence Data. Available online: https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"D184","DOI":"10.1093\/nar\/gkv1309","article-title":"GtRNAdb 2.0: An expanded database of transfer RNA genes identified in complete and draft genomes","volume":"44","author":"Chan","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_58","unstructured":"Piuco, R., and Galante, P.A.F. (2024, August 02). PiRNAdb: A Piwi-Interacting RNA Database. Available online: https:\/\/www.biorxiv.org\/content\/10.1101\/2021.09.21.461238v1."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"D152","DOI":"10.1093\/nar\/gkq1027","article-title":"miRBase: Integrating microRNA annotation and deep-sequencing data","volume":"39","author":"Kozomara","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Langmead, B., Trapnell, C., Pop, M., and Salzberg, S.L. (2009). Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome. Biol., 10.","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"ref_61","unstructured":"Pantano, L. (2024, August 02). miRTOP.github.io: Basic Structure for Home Page. Available online: https:\/\/zenodo.org\/records\/45385."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chen, Y., Chen, L., Lun, A.T.L., Baldoni, P.L., and Smyth, G.K. (2024, August 02). edgeR 4.0, Powerful Differential Analysis of Sequencing Data with Expanded Functionality and Improved Support for Small Counts and Larger Datasets. Available online: https:\/\/www.biorxiv.org\/content\/10.1101\/2024.01.21.576131v2.","DOI":"10.1101\/2024.01.21.576131"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Robinson, M.D., and Oshlack, A. (2010). A scaling normalization method for differential expression analysis of RNA-seq data. Genome. Biol., 11.","DOI":"10.1186\/gb-2010-11-3-r25"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1002\/wics.61","article-title":"Minimum covariance determinant","volume":"2","author":"Hubert","year":"2010","journal-title":"WIREs Comput Stat."},{"key":"ref_66","unstructured":"(2024, August 30). ExtraTreesClassifier. Available online: https:\/\/scikit-learn.org\/stable\/modules\/generated\/sklearn.ensemble.ExtraTreesClassifier.html#extratreesclassifier."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhang, Y., Fang, J., Xu, Z., Zhang, H., Mao, M., Chen, Y., Zhang, L., and Pian, C. (2023). NcPath: A novel platform for visualization and enrichment analysis of human non-coding RNA and KEGG signaling pathways. Bioinformatics, 39.","DOI":"10.1093\/bioinformatics\/btac812"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto Encyclopedia of Genes and Genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_69","unstructured":"Ke, G., Meng, Q., Finley, T., Wang, T., Chen, W., Ma, W., Ye, Q., and Liu, T.-Y. (2017, January 4\u20139). LightGBM: A Highly Efficient Gradient Boosting Decision Tree. Proceedings of the 31st International Conference on Neural Information Processing Systems, Long Beach, CA, USA."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8108\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:33:17Z","timestamp":1760034797000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/16\/8108"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,21]]},"references-count":69,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ijms26168108"],"URL":"https:\/\/doi.org\/10.3390\/ijms26168108","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,21]]}}}