Salivary microRNAs Identified by Small RNA Sequencing and Machine Learning as Potential Biomarkers of Alcohol Dependence

Abstract

Aim: Salivary miRNA can be easily accessible biomarkers of alcohol dependence (AD). Materials & methods: The miRNA transcriptome in the saliva of 56 African–Americans (AAs; 28 AD patients/28 controls) and 64 European–Americans (EAs; 32 AD patients/32 controls) was profiled using small RNA sequencing. Differentially expressed miRNAs were identified. Salivary miRNAs were used to predict the AD presence using machine learning with Random Forests. Results: Seven miRNAs were differentially expressed in AA AD patients, and five miRNAs were differentially expressed in EA AD patients. The AD prediction accuracy based on top five miRNAs (ranked by Gini index) was 79.1 and 72.2% in AAs and EAs, respectively. Conclusion: This study provided the first evidence that salivary miRNAs are AD biomarkers.

Keywords::

• alcohol dependence
• differential expression
• machine learning
• salivary microRNA
• small RNA sequencing

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/full/10.2217/epi-2018-0177

Author contributions

H Zhang and J Gelernter were responsible for the study concept and design. H Zhang and YZ Nunez performed the experiments. AJ Rosato, X Chen and H Zhang analyzed the data and wrote the manuscript. LA Farrer, HR Kranzler, YZ Nunez, DC Henderso and J Gelernter provided helpful comments on the manuscript. All authors critically reviewed content and approved the final version for publication.

Acknowledgments

We thank all subjects for participating in this study. We are grateful to M Cusumano, L Frederick and R Gordon at the APT foundation, CT, USA for collecting saliva samples and managing the clinical data for this study.

Financial & competing interests disclosure

This work was supported by grants (R21AA023068 and R01AA025080) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The findings achieved herein are solely the responsibility of the authors. HR Kranzler has been an advisory board member, consultant or continuing medical education speaker for Alkermes, Indivior and Lundbeck. He is a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative (ACTIVE), which was supported in the last 3 years by AbbVie, Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka and Pfizer. HR Kranzler and J Gelernter are named as inventors on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed 24 January 2018. The authors have no other relevant affiliations or financialinvolvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All participants provided written informed consent approved by the Yale University Human Investigation Committee (HIC) (Protocol #: 0102012183).

Additional information

Funding

This work was supported by grants (R21AA023068 and R01AA025080) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA). The findings achieved herein are solely the responsibility of the authors. HR Kranzler has been an advisory board member, consultant or continuing medical education speaker for Alkermes, Indivior and Lundbeck. He is a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative (ACTIVE), which was supported in the last 3 years by AbbVie, Alkermes, Amygdala Neurosciences, Arbor Pharmaceuticals, Ethypharm, Indivior, Lilly, Lundbeck, Otsuka and Pfizer. HR Kranzler and J Gelernter are named as inventors on PCT patent application #15/878,640 entitled: “Genotype-guided dosing of opioid agonists,” filed 24 January 2018. The authors have no other relevant affiliations or financialinvolvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.