scholarly journals miRNA-Based Signature Associated With Tumor Mutational Burden in Colon Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Weijie Xue ◽  
Yixiu Wang ◽  
Yuwei Xie ◽  
Chenyu Yang ◽  
Zhiqi Gong ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
Colon Adenocarcinoma ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Immune Checkpoints ◽  
Strong Positive Correlation ◽  
Positive Correlation

Colon adenocarcinoma (COAD) is one of the most common malignant tumors. Tumor mutation burden (TMB) has become an independent biomarker for predicting the response to immune checkpoint inhibitors (ICIs). miRNAs play an important role in cancer-related immune regulation. However, the relationship between miRNA expression and TMB in COAD remains unclear. Therefore, the transcriptome profiling data, clinical data, mutation annotation data, and miRNA expression profiles for cases of COAD were downloaded from the TCGA database. Subsequently, 323 COAD cases were randomly divided into training and test sets. The differential expression of miRNAs in the high and low TMB groups in the training set was obtained as a signature using the least absolute shrinkage and selection operator (LASSO) logistic regression and verified in the test set. Based on the LASSO method, principal component analysis (PCA), and ROC, we found that the signature was credible because it can discriminate between high and low TMB levels. In addition, the correlation between the 18-miRNA-based signature and immune checkpoints was performed, followed by qRT-PCR, to measure the relative expression of 18 miRNAs in COAD patients. The miRNA-based model had a strong positive correlation with TMB and a weak positive correlation with CTLA4 and CD274 (PD-L1). However, no correlation was observed between the model and SNCA (PD-1). Finally, enrichment analysis of the 18 miRNAs was performed to explore their biological functions. The results demonstrated that 18 miRNAs were involved in the process of immunity and cancer pathways. In conclusion, the 18-miRNA-based signature can effectively predict and discriminate between the different TMB levels of COAD and provide a guide for its treatment with ICIs.

scholarly journals A MiRNA-based Signature is Associated With Tumor Mutational Burden in Colon Adenocarcinoma

2020 ◽  
Author(s):  
Weijie xue ◽  
Yixiu Wang ◽  
Zhiqi Gong ◽  
Chenyu Yang ◽  
Yuwei Xie ◽  
...  
Keyword(s):  
Principal Component Analysis ◽  
Differential Expression ◽  
Colon Adenocarcinoma ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Component Analysis ◽  
Immune Checkpoints ◽  
Training Set ◽  
Test Set ◽  
Lasso Method

Abstract Background:Tumor mutation burden (TMB) has become an independent biomarker for predicting the response of Immune checkpoint inhibitors.MiRNA plays an important role in cancer-related immune regulation but the relationship between expression of miRNA and TMB is unclear in colon adenocarcinoma (COAD).Method:The transcriptome profiling data, clinical data, mutation annotation data and miRNA expression profiles for cases with COAD were downloaded from TCGA database, and then COAD samples were randomly divided into training set and test set. The differential expression miRNAs of high and low TMB group in training set was obtained as a signature by the least absolute shrinkage and selection operator (LASSO) logistic regression, and it was verified in test set. UsingLASSO method, principal component analysis (PCA) and ROC to verify the credibility of signature.In addition, the correlation betweenthemiRNA-based signature and immune checkpoints was performed.In the end, enrichment analysis of the miRNAs in signature was performed to explore the biological function.Results:18 differential expression miRNAswere obtainedaccording to LASSO method. According to LASSO method, principal component analysis (PCA) and ROC, we found that the credibility of signature, and the signature can discriminate the high and low TMB level. Furthermore, the results of correlation between the 18-miRNA-based signature and immune checkpoints showed that the miRNA-based model has a strong positive correlation with TMB, weak positive correlation with CTLA4 and CD274 (PD-L1). However, there is no correlation between the model and SNCA (PD-1).Finally, enrichment analysis of the 18miRNAs demonstrated that the 18 miRNAs were involved in process of immunity and cancer pathways.Conclusion:We established a novel miRNA-based signature integrating expression of miRNAs and TMB levels. The 18-miRNA-based signature can effectively predict and discriminate the TMB levels in COAD, and provides apotential guide of ICIs treatment.

scholarly journals Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Xu ◽  
Qing Zheng
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Validation Cohort ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Immune Checkpoints ◽  
Positive Correlation ◽  
Expression Signature ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.

Comprehensive Pan-Cancer Analysis on CBX3 as a Prognostic and Immunological Biomarker

2021 ◽  
Author(s):  
Hongjuan Niu ◽  
Peiqiong Chen ◽  
Lu Fan ◽  
Boyu Sun
Keyword(s):  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Immune Checkpoints ◽  
Protein Levels ◽  
Carcinoma Colon ◽  
Infiltrating Lymphocytes ◽  
Functional Mechanisms ◽  
Immune Score ◽  
Pan Cancer

Abstract Background: Increased evidence supports the relationship between chromobox protein homolog 3 (CBX3) and tumorigenesis of some cancers. However, the role of CBX3 in pan-cancers remains poorly defined. In the research, we aimed to investigate the prognostic value and the immunological functions of CBX3. Results: We explored the potential oncogenic roles of CBX3 in mRNA and protein levels based on the diverse databases, including the expression, the correlation with prognosis, tumor microenvironment (TME), DNA methylation, protein phosphorylation and enrichment analysis across all TCGA tumors. The results show that CBX3 is overexpressed in multiple cancers, and significant correlations exist between high expression and adverse prognosis in most tumor patients. We observed an enhanced phosphorylation level in uterine corpus endometrial carcinoma, colon cancer and lung adenocarcinoma. A distinct relationship was also found between CBX3 expression and TME, including immune infiltration of tumor-infiltrating lymphocytes (TILs) and cancer-associated fibroblasts (CAFs), immune score or matrix score, immune checkpoints. The correlative transcription factors and miRNAs of CBX3-binding hub genes were analyzed to investigate the molecular mechanism. Moreover, alcoholism and alteration of DNA cellular biology may be involved in the functional mechanisms of CBX3. Conclusion: The first pan-cancer study offers a relatively comprehensive cognition on the oncogenic roles of CBX3 as a prognostic and immunological marker in various malignant tumors.

scholarly journals Identifying Hypoxia Characteristics to Stratify Prognosis and Assess the Tumor Immune Microenvironment in Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhenan Zhang ◽  
Qinhan Li ◽  
Feng Wang ◽  
Binglei Ma ◽  
Yisen Meng ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Immune Checkpoint Inhibitors ◽  
Risk Model ◽  
Checkpoint Inhibitors ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Risk Groups ◽  
Immune Microenvironment ◽  
Related Risk

Background: Renal cell carcinoma (RCC) is a common malignant tumor worldwide, and immune checkpoint inhibitors are a new therapeutic option for metastatic RCC. Infiltrating immune cells in the tumor microenvironment (TME) play a critical part in RCC biology, which is important for tumor therapy and prediction. Hypoxia is a common condition that occurs in the TME and may lead to RCC immunosuppression and immune escape. This study was conducted to analyze the extent of the hypoxia immune microenvironment in the TME of RCC and develop a hypoxia-related risk model for predicting the prognosis of patients with RCC.Methods: The gene expression profiles of 526 patients with RCC were downloaded from The Cancer Genome Atlas database. Combined with the hallmark-hypoxia gene dataset downloaded from Gene Set Enrichment Analysis, prognosis-related hypoxia genes were selected by survival analysis. A protein–protein interaction network and functional enrichment analysis were performed. A hypoxia-related risk model predicting the prognosis of patients with RCC was established using the least absolute shrinkage and selection operator. Data of 91 cases downloaded from the International Cancer Genome Consortium (ICGC) database were used for validation. CIBERSORT was applied to analyze the fractions of 22 immune cell types in the TME of RCC between low- and high-risk groups. The expression profiles of immunomodulators and immunosuppressive cytokines were also analyzed.Results: Ninety-three genes were significantly associated with poor overall survival of patients with RCC and were mainly involved in 10 pathways. Using the established hypoxia-related risk model, the receiver operating characteristic curves showed an accuracy of 76.1% (95% CI: 0.719–0.804), and Cox proportional hazards regression analysis revealed that the model was an independent predictor of the prognosis of patients with RCC [hazard ratio (HR) = 2.884; 95% CI: 2.090–3.979] (p &lt; 0.001). Using the ICGC database, we verified that the low-risk score group had a better overall survival outcome than the high-risk group. Additionally, dividing the hypoxia risk score into high-risk and low-risk groups could predict the immune microenvironment of RCC.Conclusions: We demonstrated that a hypoxia-related risk model can be used to predict the outcomes of patients with RCC and reflect the immune microenvironment of RCC, which may help improve the overall clinical response to immune checkpoint inhibitors.

scholarly journals The High Expression of CD276/HAVCR2 and CD163 is an Adverse Immune Subtype of Glioblastoma and is Closely Related to Epithelial-Mesenchymal Transition

2020 ◽  
Author(s):  
Xiaohong Hou ◽  
Guiyin Zhou ◽  
Yinchun Fan ◽  
Qiang Zhang ◽  
Chengming Xiang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Enrichment Analysis ◽  
R Package ◽  
High Expression ◽  
Sequencing Data ◽  
Mesenchymal Transition ◽  
Patient Prognosis

Abstract Background Glioblastoma (GBM) is one of the most malignant tumors that can afflict the central nervous system. Previous studies have observed that there are individual differences in the treatment response of immune checkpoint inhibitors in glioblastoma. This study’s aim is to ascertain the factors that may affect the efficacy of immunosuppressant therapy. Methods The clinical data of this study were obtained from a public database. Then, the data was analyzed and processed by R software and corresponding R package. To verify the results of the analysis, information was gathered from 89 GBM patients in our hospital and thereafter the corresponding paraffin sections were stained and quantitatively analyzed by immunohistochemistry. Results From the analysis, it was observed that both CD276 and HAVCR2 were significantly overexpressed in GBM and could be associated with patient prognosis. The analysis of single cell RNA sequencing data and GBM data analysis found an immune subtype with poor prognosis. Further analysis found that the high expression of CD276, HAVCR2 and CD163 was closely related to epithelial-mesenchymal transition (EMT) and could affect the patient prognosis of PD-L1 high expression. GSVA enrichment analysis showed that CD276, HAVCR2 and CD163 might induce EMT by JAK-STAT3 signaling pathway, and RUNX1 and IKZF1 might be transcription factors that regulate CD276/HAVCR2 high expression. Conclusions We found an immune subtype with poor prognosis of GBM, the high expression of CD276, HAVCR2 and CD163 with EMT are closely related and may be one of the factors affecting the efficacy of Anti-PD-L1.

scholarly journals Identification of Novel COVID-19 Biomarkers by Multiple Feature Selection Strategies

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Shuai Zhang ◽  
Renliang Qu ◽  
Pengyan Wang ◽  
Shenghan Wang
Keyword(s):  
Feature Selection ◽  
Expression Profiles ◽  
Feature Selection Method ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Nucleic Acid Detection ◽  
Support Vector ◽  
New Biomarkers ◽  
Optimal Feature

Coronavirus disease 2019 (COVID-19) arising from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a global pandemic since its first report in December 2019. So far, SARS-CoV-2 nucleic acid detection has been deemed as the golden standard of COVID-19 diagnosis. However, this detection method often leads to false negatives, thus triggering missed COVID-19 diagnosis. Therefore, it is urgent to find new biomarkers to increase the accuracy of COVID-19 diagnosis. To explore new biomarkers of COVID-19 in this study, expression profiles were firstly accessed from the GEO database. On this basis, 500 feature genes were screened by the minimum-redundancy maximum-relevancy (mRMR) feature selection method. Afterwards, the incremental feature selection (IFS) method was used to choose a classifier with the best performance from different feature gene-based support vector machine (SVM) classifiers. The corresponding 66 feature genes were set as the optimal feature genes. Lastly, the optimal feature genes were subjected to GO functional enrichment analysis, principal component analysis (PCA), and protein-protein interaction (PPI) network analysis. All in all, it was posited that the 66 feature genes could effectively classify positive and negative COVID-19 and work as new biomarkers of the disease.

scholarly journals A case report of immune-related pneumonitis after combined treatment of non small cell lung cancer

2020 ◽  
pp. 258-264
Author(s):  
E. S. Denisova ◽  
M. S. Ardzinba ◽  
K. K. Laktionov ◽  
D. I. Yudin ◽  
K. A. Sarantseva ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Left Lung ◽  
Immune Checkpoints ◽  
Results Of Treatment ◽  
Predictors Of Response ◽  
High Doses

Immunotherapy is the most promising method in the treatment of lung cancer, especially in connection with the rapidly growing development of monoclonal antibodies aimed at inhibiting immune checkpoints: anti-CTLA-4, anti-PD-1, anti-PD-L1. Classic immuno-mediated adverse events that occur with this method of treatment can affect several organs, including the lungs. Pneumonitis is a potentially life-threatening complication and often requires rapid treatment with high doses of corticosteroids and antibacterial drugs. We present the case of a 67-year-old patient with primary multiple malignant tumors of the larynx and left lung after combined treatment and incomplete treatment with Nivolumab, complicated by immuno-mediated pneumonitis. This report highlights the importance of treating patients with contraindications to chemotherapy when specific antitumor treatment is required, as well as timely detection of a rare but dangerous adverse event: immuno-mediated pneumonitis that occurs during treatment with immune checkpoint inhibitors. Thus, knowing the frequency of adverse events when using PD-1 and PD-L1 inhibitors, as well as the possible presence of comorbidities in patients, will make it easier for doctors to make informed decisions in the treatment of patients, and understanding the interaction of the tumor and the immune system will help determine the best predictors of response and further improve the results of treatment of patients with NSCLC.

scholarly journals miRNA profiles of canine cutaneous mast cell tumours with early nodal metastasis and evaluation as potential biomarkers

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Valentina Zamarian ◽  
Roberta Ferrari ◽  
Damiano Stefanello ◽  
Fabrizio Ceciliani ◽  
Valeria Grieco ◽  
...  
Keyword(s):  
Factor Analysis ◽  
Mast Cell ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Nodal Metastasis ◽  
Pathway Enrichment Analysis ◽  
Multiple Factor Analysis ◽  
Cutaneous Mast Cell ◽  
Multiple Factor

Abstract Cutaneous mast cell tumours (MCTs) are common skin neoplasms in dogs. MicroRNAs (miRNAs) are post-transcriptional regulators involved in several cellular processes, and they can function as tumour promoters or suppressors. However, the role of miRNAs in canine MCTs has not yet been elucidated. Thus, the current study aimed to characterize miRNA profiles and to assess their value as biomarkers for MCTs. miRNA expression profiles were assessed in formalin-fixed, paraffin-embedded samples by next-generation sequencing. Ten samples were MCT tissues, and 7 were healthy adjacent tissues. Nine dysregulated miRNAs (DE-miRNAs) were then validated using RT-qPCR in a larger group of MCT samples, allowing the calculation of ROC curves and performance of multiple factor analysis (MFA). Pathway enrichment analysis was performed to investigate miRNA biological functions. The results showed that the expression of 63 miRNAs (18 up- and 45 downregulated) was significantly affected in MCTs. Five DE-miRNAs, namely, miR-21-5p, miR-92a-3p, miR-338, miR-379 and miR-885, were validated by RT-qPCR. The diagnostic accuracy of a panel of 3 DE-miRNAs—miR-21, miR-379 and miR-885—exhibited increased efficiency in discriminating animals with MCTs (AUC = 0.9854) and animals with lymph node metastasis (AUC = 0.8923). Multiple factor analysis revealed clusters based on nodal metastasis. Gene Ontology and KEGG analyses confirmed that the DE-miRNAs were involved in cell proliferation, survival and metastasis pathways. In conclusion, the present study demonstrated that the miRNA expression profile is changed in the MCT microenvironment, suggesting the involvement of the altered miRNAs in the epigenetic regulation of MCTs and identifying miR-21, miR-379 and miR-885 as promising biomarkers.

scholarly journals Integrative Analysis of MicroRNA and mRNA Sequencing Data Identifies Novel Candidate Genes and Pathways for Developmental Dysplasia of Hip

Cartilage ◽  
2021 ◽  
pp. 194760352199085
Author(s):  
Bolun Cheng ◽  
Yumeng Jia ◽  
Yan Wen ◽  
Weikun Hou ◽  
Ke Xu ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Developmental Dysplasia ◽  
Integrative Analysis ◽  
Skeletal System ◽  
Difference Analysis ◽  
Developmental Dysplasia Of Hip ◽  
Mirna Expression Profiles

Objective Our aim is to explore the candidate pathogenesis genes and pathways of developmental dysplasia of hip (DDH). Design Proliferating primary chondrocytes from hip cartilage were used for total RNA extraction including 5 DDH patients and 5 neck of femur fracture (NOF) subjects. Genome-wide mRNA and microRNA (miRNA) were then sequenced on the Illumina platform (HiSeq2500). Limma package was used for difference analysis of mRNA expression profiles. edgeR was used for difference analysis of miRNA expression profiles. miRanda was used to predict miRNA-target genes. The overlapped DDH associated genes identified by mRNA and miRNA integrative analysis were further compared with the differently expressed genes in hip osteoarthritis (OA) cartilage. Results Differential expression analysis identified 1,833 differently expressed mRNA and 186 differently expressed miRNA for DDH. Integrative analysis of mRNA and miRNA expression profiles identified 175 overlapped candidate genes (differentially expressed genes, DEGs) for DDH, such as VWA1, TMEM119, and SCUBE3. Further gene ontology enrichment analysis detected 111 candidate terms for DDH, such as skeletal system morphogenesis ( P = 4.92 × 10−5) and skeletal system development ( P = 8.85 × 10−5). Pathway enrichment analysis identified 14 candidate pathways for DDH, such as Hedgehog signaling pathway ( P = 4.29 × 10−5) and Wnt signaling pathway ( P = 4.42 × 10−2). Among the identified DDH associated candidate genes, we also found some genes were detected in hip OA including EFNA1 and VWA1. Conclusions We identified multiple novel candidate genes and pathways for DDH, providing novel clues for understanding the molecular mechanism of DDH.

scholarly journals Interplay between Phenotypic Resistance to Relevant Antibiotics in Gram-Negative Urinary Pathogens: A Data-Driven Analysis of 10 Years’ Worth of Antibiogram Data

Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1059
Author(s):  
Márió Gajdács ◽  
Zoltán Bátori ◽  
Katalin Burián
Keyword(s):  
Secondary Analysis ◽  
Principal Component ◽  
Critical Issue ◽  
Strong Positive Correlation ◽  
Gram Negative ◽  
Positive Correlation ◽  
Phenotypic Resistance ◽  
Positive Correlations ◽  
Tract Infections ◽  
Resistance Data

The global emergence of antimicrobial resistance (AMR) has become a critical issue for clinicians, as it puts the decades of developments in the medical field in jeopardy, by severely limiting the useful therapeutic arsenal of drugs, both in nosocomial and community-acquired infections. In the present study, a secondary analysis of taxonomic and resistance data was performed, corresponding to urinary tract infections (UTIs) caused by Gram-negative bacteria, detected between 1 January 2008 to 31 December 2017 at the Albert Szent-Györgyi Health Center, University of Szeged. The following were identifiable from the data collected: year of isolation; outpatient (OP)/inpatient (IP) origin of the isolate; taxonomy; and susceptibility/resistance to selected indicator antibiotics. Principal component analysis (PCA) and a correlation matrix were used to determine the association between the presences of resistance against indicator antibiotics in each taxonomic group. Overall, data from n = 16,240 outpatient and n = 13,964 inpatient Gram-negative UTI isolates were included in the data analyses. In E. coli, strong positive correlations were seen between resistance to ciprofloxacin (CIP) and gentamicin (GEN) resistance (OP: r = 0.6342, p = 0.049; IP: r = 0.9602, p < 0.001), whereas strong negative correlations were shown for fosfomycin (FOS) and nitrofurantoin (NIT) resistance (OP: r= −0.7183, p = 0.019; IP: r= −0.7437; p = 0.014). For Klebsiella spp. isolates, CIP resistance showed strong positive correlation with resistance to third-generation cephalosporins (3GC) and GEN (r = 0.7976, p = 0.006 and r = 0.7428, p = 0.014, respectively) in OP isolates, and with resistance to trimethoprim-sulfamethoxazole (SXT) and FOS (r = 0.8144, p = 0.004 and r = 0.7758, p < 0.001, respectively) in IP isolates. For members of the Citrobacter-Enterobacter-Serratia group, the resistance among indicator antibiotics showed a strong positive correlation, with the exception of FOS resistance. In the Proteus-Providencia-Morganella group, the strongest association was noted between CIP and SXT resistance (OP: r = 0.9251, p < 0.001; IP: r = 0.8007; p = 0.005). In the case of OP Acinetobacter spp., CIP showed strong and significant positive correlations with most indicator antibiotics, whereas for IP isolates, strong negative correlations arose among imipenem (IMI) resistance and resistance to other drugs. For Pseudomonas spp., strong and positive correlations were noted among resistance to β-lactam antibiotics and aminoglycosides, with the exception of ceftazidime (CEFT), showing strong, but negative correlations. Though molecular tests and sequencing-based platforms are now considered as the gold-standard for AMR surveillance, standardized collection of phenotypic resistance data and the introduction of Big Data analytic methods may be a viable alternative for molecular surveillance, especially in low-resource settings.

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