Br J Surg. 2023 Feb 2:znad019. doi: 10.1093/bjs/znad019. Online ahead of print.

NO ABSTRACT

PMID:36726208 | DOI:10.1093/bjs/znad019

Biol Pharm Bull. 2023;46(2):163-169. doi: 10.1248/bpb.b22-00569.

ABSTRACT

Phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) is a highly conserved enzyme that generates phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) by phosphorylating phosphatidylinositol 4-phosphate (PI(4)P). Schizosaccharomyces pombe (S. pombe) its3-1 is a loss-of-function mutation in the essential its3+ gene that encodes a PI4P5K. Its3 regulates cell proliferation, cytokinesis, cell integrity, and membrane trafficking, but little is known about the regulatory mechanisms of Its3. To identify regulators of Its3, we performed a genetic screening utilizing the high-temperature sensitivity (TS) of its3-1 and identified puf3+ and puf4+, encoding Pumilio/PUF family RNA-binding proteins as multicopy suppressors of its3-1 cells. The deletions of the PUF domains in the puf3+ and puf4+ genes resulted in the reduced ability to suppress its3-1, suggesting that the suppression by Puf3 and Puf4 may involve their RNA-binding activities. The gene knockout of Puf4, but not that of Puf3, exacerbated the TS of its3-1. Interestingly, mutant Its3 expression levels both at mRNA and protein levels were lower than those of the wild-type (WT) Its3. Consistently, the overexpression of the mutant its3-1 gene suppressed the its3-1 phenotypes. Notably, Puf3 and Puf4 overexpression increased the mRNA and protein expression levels of both Its3 and Its3-1. Collectively, our genetic screening revealed a functional relationship between the Pumilio/PUF family RNA-binding proteins and PI4P5K.

PMID:36724944 | DOI:10.1248/bpb.b22-00569

Biol Pharm Bull. 2023;46(2):138. doi: 10.1248/bpb.b23-ctf4602.

NO ABSTRACT

PMID:36724940 | DOI:10.1248/bpb.b23-ctf4602

Singapore Med J. 2023 Jan;64(1):59-66. doi: 10.4103/singaporemedj.SMJ-2021-438.

ABSTRACT

Advancements in high-throughput sequencing have yielded vast amounts of genomic data, which are studied using genome-wide association study (GWAS)/phenome-wide association study (PheWAS) methods to identify associations between the genotype and phenotype. The associated findings have contributed to pharmacogenomics and improved clinical decision support at the point of care in many healthcare systems. However, the accumulation of genomic data from sequencing and clinical data from electronic health records (EHRs) poses significant challenges for data scientists. Following the rise of artificial intelligence (AI) technology such as machine learning and deep learning, an increasing number of GWAS/PheWAS studies have successfully leveraged this technology to overcome the aforementioned challenges. In this review, we focus on the application of data science and AI technology in three areas, including risk prediction and identification of causal single-nucleotide polymorphisms, EHR-based phenotyping and CRISPR guide RNA design. Additionally, we highlight a few emerging AI technologies, such as transfer learning and multi-view learning, which will or have started to benefit genomic studies.

PMID:36722518 | DOI:10.4103/singaporemedj.SMJ-2021-438

Int J Pharm Compd. 2023 Jan-Feb;27(1):12-21.

ABSTRACT

COVID-19 (coronavirus disease 2019), which is caused by the positive-stranded ribonucleic acid virus SARS-CoV-2 (acute respiratory syndrome coronavirus 2), is an extremely contagious airborne illness of pandemic proportions. In the modern era, few diseases other than COVID-19 have produced such severe, prolific, and protean short-term adverse effects and long-term sequelae. In addition, few other pandemics have exhibited a trajectory of morbidity and mortality so affected by social, economic, and political factors as well as individual personal perceptions and beliefs. Vaccines for the prevention of SARS-CoV-2 infection and treatments for COVID-19 mitigate associated morbidity and mortality, but an increasing array of variants presents challenges to therapeutic effectiveness. As a result, afflicted patients often require customized treatments that address the severity of their infection, the manifestations of disease they exhibit, and their individual pharmacogenomic profile. In such cases, a compounded preparation may offer needed support for recovery. This article, which is the first in a series on compounding for COVID-19 and long COVID (i.e., the long- term sequelae of SARS-CoV-2 infection), provides information about pertinent viral terminology and a brief overview of SARS-CoV-2 mutations and variants of note. Two formulations for customized compounds that may prove effective in treating the acute and/or long-term effects of COVID-19 when commercial therapies have failed are also provided.

PMID:36720058

Yonsei Med J. 2023 Feb;64(2):77-86. doi: 10.3349/ymj.2022.0316.

ABSTRACT

Although the majority of individuals with hypertension (HTN) have primary and polygenic HTN, monogenic HTN is a secondary type that is widely thought to play a key role in pediatric HTN, which has the characteristics of early onset, refractory HTN with a positive family history, and electrolyte disorders. Monogenic HTN results from single genetic mutations that contribute to the dysregulation of blood pressure (BP) in the kidneys and adrenal glands. It is pathophysiologically associated with increased sodium reabsorption in the distal tubule, intravascular volume expansion, and HTN, as well as low renin and varying aldosterone levels. Simultaneously increased or decreased potassium levels also provide clues for the diagnosis of monogenic HTN. Discovering the genetic factors that cause an increase in BP has been shown to be related to the choice of and responses to antihypertensive medications. Therefore, early and precise diagnosis with genetic sequencing and effective treatment with accurate antihypertensive agents are critical in the management of monogenic HTN. In addition, understanding the genetic architecture of BP, causative molecular pathways perturbing BP regulation, and pharmacogenomics can help with the selection of precision and personalized medicine, as well as improve morbidity and mortality in adulthood.

PMID:36719014 | DOI:10.3349/ymj.2022.0316

Pharmacogenomics. 2023 Jan 31. doi: 10.2217/pgs-2022-0159. Online ahead of print.

ABSTRACT

Aim: To evaluate the association between CYP2C19, CYP3A4 and ABCC2 polymorphisms and voriconazole plasma concentrations in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation. Materials & methods: High performance liquid chromatography-mass spectrometry was employed to monitor voriconazole concentrations. First-generation sequencing was performed to detect gene polymorphisms. Results: Voriconazole concentrations of normal metabolizers were significantly higher than those of intermediate (p < 0.05) and ultrafast (p < 0.001) metabolizers. Patients with ABCC2 GG and GA genotypes exhibited significantly lower voriconazole concentrations compared with patients with the AA genotype (p < 0.05). Conclusion: These results demonstrate a significant association between voriconazole concentrations and the CYP2C19 phenotype in Uygur pediatric patients with allogeneic hematopoietic stem cell transplantation.

PMID:36718992 | DOI:10.2217/pgs-2022-0159

Pharmacogenomics. 2023 Jan 31. doi: 10.2217/pgs-2022-0156. Online ahead of print.

ABSTRACT

Aim: To evaluate the association between genetic polymorphisms and plasma concentration-to-dose ratio of valproic acid (CDRV) in Chinese epileptic patients. Methods: A total of 46 epileptic patients treated with valproic acid therapy were enrolled. 18 SNPs in nine genes related to valproic acid were directly sequenced with Sanger methods. Results: Patients carrying UGT1A6 heterozygous genotypes had significantly lower CDRV than those carrying the wild-type genotypes. In contrast, patients with the homozygote genotypes of CYP2C9 and ABAT had higher CDRV than those with the wild-type genotypes, and patients with the heterozygous genotypes of CYP2C19 had higher CDRV. Conclusion: Detection of genetic polymorphism in these genes might facilitate an appropriate dose of valproic acid for epileptic patients. Further studies with larger cohorts are necessary to underpin these observations.

PMID:36718958 | DOI:10.2217/pgs-2022-0156

Oncologist. 2023 Jan 30:oyac277. doi: 10.1093/oncolo/oyac277. Online ahead of print.

ABSTRACT

Patients experience interindividual variation in response to analgesics, which may be partially explained by genetics. This commentary discusses a recently published trial on COMT genotype and opioid dose requirements and describes the potential role for COMT and other genes (eg, CYP2D6) on opioid therapy and the current evidence for germline pharmacogenetics and resources for opioid pharmacogenetics.

PMID:36718020 | DOI:10.1093/oncolo/oyac277

Hereditas. 2023 Jan 31;160(1):3. doi: 10.1186/s41065-023-00264-1.

ABSTRACT

BACKGROUND: Functional mutations or polymorphisms affecting forkhead box P3 (FOXP3) can lead to their abnormal FOXP3 gene expression and/or defective Treg cells generation, thus resulting in autoimmune disease and inflammatory disorders. FOXP3 also plays a key role in Type 2 diabetes mellitus (T2DM) and its complications, because the disease usually involves chronic low-grade inflammatory disorders and is associated with long-term immune system imbalance. This study aimed to investigate the association between FOXP3 polymorphisms and the susceptibility to T2DM and type 2 diabetes nephropathy (T2DN) within the Han Chinese populations.

METHODS: Polymorphisms in rs3761548C/A and rs2294021C/T were examined in 400 patients (which include an equal number of T2DM and T2DN groups) and 200 healthy controls using PCR-HRM and sequence analysis.

RESULTS: The genotype and allelic frequencies of the two single nucleotide polymorphisms (SNPs) were significantly different in T2DM and the progression of diabetes developing to T2DN. The further gender-based evaluation showed that in female subjects, rs3761548C/A was associated with an approximately 3-fold higher threat for T2DM and 4.5-fold for T2DN, while there was no noticeable association with rs2294021C/T; in males, the promoter polymorphism showed an increased predisposition of 5.4-fold and 3.4-fold predisposition to T2DM and T2DN, respectively, while rs2294021 polymorphism could impart a nearly 2-fold risk of developing T2DN. An additional analysis of combined genotypes (rs3761548 C/A-rs2294021C/T) revealed that CC-CC and CC-CT can be considered protective combinations in the predisposition of males with diabetes towards T2DN, while AA-CC and AA-TT have the opposite effect.

CONCLUSIONS: This study demonstrated the possible involvement of individual and combined genetic associations of rs3761548C/A and rs2294021C/T polymorphisms with the susceptibility to diabetes and diabetic nephropathy in the Han Chinese population, as well as gender bias.

PMID:36717877 | DOI:10.1186/s41065-023-00264-1

J Exp Clin Cancer Res. 2023 Jan 30;42(1):37. doi: 10.1186/s13046-023-02606-3.

ABSTRACT

BACKGROUND: A pharmacogenomic platform using patient-derived cells (PDCs) was established to identify the underlying resistance mechanisms and tailored treatment for patients with advanced or refractory lung cancer.

METHODS: Drug sensitivity screening and multi-omics datasets were acquired from lung cancer PDCs (n = 102). Integrative analysis was performed to explore drug candidates according to genetic variants, gene expression, and clinical profiles.

RESULTS: PDCs had genomic characteristics resembled with those of solid lung cancer tissues. PDC molecular subtyping classified patients into four groups: (1) inflammatory, (2) epithelial-to-mesenchymal transition (EMT)-like, (3) stemness, and (4) epithelial growth factor receptor (EGFR)-dominant. EGFR mutations of the EMT-like subtype were associated with a reduced response to EGFR-tyrosine kinase inhibitor therapy. Moreover, although RB1/TP53 mutations were significantly enriched in small-cell lung cancer (SCLC) PDCs, they were also present in non-SCLC PDCs. In contrast to its effect in the cell lines, alpelisib (a PI3K-AKT inhibitor) significantly inhibited both RB1/TP53 expression and SCLC cell growth in our PDC model. Furthermore, cell cycle inhibitors could effectively target SCLC cells. Finally, the upregulation of transforming growth factor-β expression and the YAP/TAZ pathway was observed in osimertinib-resistant PDCs, predisposing them to the EMT-like subtype. Our platform selected XAV939 (a WNT-TNKS-β-catenin inhibitor) for the treatment of osimertinib-resistant PDCs. Using an in vitro model, we further demonstrated that acquisition of osimertinib resistance enhances invasive characteristics and EMT, upregulates the YAP/TAZ-AXL axis, and increases the sensitivity of cancer cells to XAV939.

CONCLUSIONS: Our PDC models recapitulated the molecular characteristics of lung cancer, and pharmacogenomics analysis provided plausible therapeutic candidates.

PMID:36717865 | DOI:10.1186/s13046-023-02606-3

J Int Med Res. 2023 Jan;51(1):3000605231153764. doi: 10.1177/03000605231153764.

ABSTRACT

By the end of 2022, there had been a reduction in new cases and deaths caused by coronavirus disease 2019 (COVID-19). At the same time, new variants of the severe acute respiratory syndrome coronavirus 2 virus were being discovered. Critically ill patients with COVID-19 have been found to have high serum levels of proinflammatory cytokines, especially interleukin (IL)-6. COVID-19-related mortality has been attributed in most cases to the cytokine storm caused by increased levels of inflammatory cytokines. Dexamethasone in low doses and immunomodulators such as IL-6 inhibitors are recommended to overcome the cytokine storm. This current narrative review highlights the place of other therapeutic choices such as proteasome inhibitors, protease inhibitors and nuclear factor kappa B inhibitors in the treatment of patients with COVID-19.

PMID:36717541 | DOI:10.1177/03000605231153764

Am J Health Syst Pharm. 2023 Jan 28:zxad025. doi: 10.1093/ajhp/zxad025. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: We describe the implementation of CYP2D6-focused pharmacogenetic testing to guide opioid prescribing in a quaternary care, nonprofit pediatric academic medical center.

SUMMARY: Children are often prescribed oral opioids after surgeries, for cancer pain, and occasionally for chronic pain. In 2004, Cincinnati Children's Hospital Medical Center implemented pharmacogenetic testing for CYP2D6 metabolism phenotype to inform codeine prescribing. The test and reports were updated to align with changes over time in the testing platform, the interpretation of genotype to phenotype, the electronic health record, and Food and Drug Administration guidance. The use of the test increased when a research project required testing and decreased as prescribing of oxycodone increased due to FDA warnings about codeine. Education about opioid-focused pharmacogenetic test was provided to prescribers (eg, the pain and sickle cell teams) as well as patients and families. Education and electronic health record capability increased provider compliance with genotype-guided postsurgical prescribing of oxycodone, although there was a perceived lack of utility for oxycodone prescribing.

CONCLUSION: The implementation of pharmacogenetic testing to inform opioid prescribing for children has evolved with accumulating evidence and guidelines, requiring changes in reporting of results and recommendations.

PMID:36715063 | DOI:10.1093/ajhp/zxad025

Front Pharmacol. 2023 Jan 12;14:1055991. doi: 10.3389/fphar.2023.1055991. eCollection 2023.

ABSTRACT

Introduction: Most hepatically cleared drugs are metabolized by cytochromes P450 (CYPs), and Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provide curated clinical references for CYPs to apply individual genome data for optimized drug therapy. However, incorporating novel pharmacogenetic variants into guidelines takes considerable time. Methods: We comprehensively assessed the drug metabolizing capabilities of CYP2C19 variants discovered through population sequencing of two substrates, S-mephenytoin and omeprazole. Results: Based on established functional assays, 75% (18/24) of the variants not yet described in Pharmacogene Variation (PharmVar) had significantly altered drug metabolizing capabilities. Of them, seven variants with inappreciable protein expression were evaluated as protein damaging by all three in silico prediction algorithms, Sorting intolerant from tolerant (SIFT), Polymorphism Phenotyping v2 (PolyPhen-2), and Combined annotation dependent depletion (CADD). The five variants with decreased metabolic capability (<50%) of wild type for either substrates were evaluated as protein damaging by all three in silico prediction algorithms, except CADD exact score of NM_000769.4:c.593T>C that was 19.68 (<20.0). In the crystal structure of the five polymorphic proteins, each altered residue of all those proteins was observed to affect the key structures of drug binding specificity. We also identified polymorphic proteins indicating different tendencies of metabolic capability between the two substrates (5/24). Discussion: Therefore, we propose a methodology that combines in silico prediction algorithms and functional assays on polymorphic CYPs with multiple substrates to evaluate the changes in the metabolism of all possible genomic variants in CYP genes. The approach would reinforce existing guidelines and provide information for prescribing appropriate medicines for individual patients.

PMID:36713839 | PMC:PMC9877350 | DOI:10.3389/fphar.2023.1055991

Front Genet. 2023 Jan 13;13:1085994. doi: 10.3389/fgene.2022.1085994. eCollection 2022.

ABSTRACT

Introduction: Pharmacogenetic testing may hold promise in addressing health disparities, as medically underserved patients appear to be prescribed medications with pharmacogenetic guidelines at higher rates. While routine clinical implementation of testing in medically underserved populations has not yet been achieved, using patient perspectives to inform implementation should increase the likelihood of success. The aim of this study was to assess the perceptions, knowledge, and attitudes regarding pharmacogenetic testing in medically underserved patients. Methods: We developed a survey instrument to assess respondent views on pharmacogenetic testing. The survey instrument was developed through a process of literature review, expert input, iterative pilot testing, and final refinement. The survey instrument was fielded to US adults with an estimated household income of $42,000 per year or less. Results: During the survey instrument development, 59 pilot testers provided 133 comments which lead to 38 revisions to the survey instrument. The nationwide survey resulted in 1,060 respondents, of which half (49.8%) reported having no health insurance or being on Medicaid. Most patients (78.9%) had not previously heard of pharmacogenetic testing. After being provided an explanation of pharmacogenetic testing, 60.5% were very or moderately interested in receiving testing if there were no cost and 75.8% of respondents agreed or strongly agreed that pharmacogenetic testing should be available to help with medication selection regardless of cost. Respondents shared that their greatest concern with pharmacogenetic testing was that the test would cost them money, which was expressed by over half (52.7%). This was followed by concerns that the results could reveal a risk for a disease, could affect health insurance, and would not improve care. Discussion: Our results indicate a strong interest in pharmacogenetic testing and identify key perceptions, attitudes, concerns, and potential barriers that can be addressed as pharmacogenetic testing is clinically implemented in medically underserved patient populations.

PMID:36712853 | PMC:PMC9880414 | DOI:10.3389/fgene.2022.1085994

Pharmacogenomics J. 2023 Jan 28. doi: 10.1038/s41397-023-00299-7. Online ahead of print.

ABSTRACT

Tumor DNA sequencing is becoming standard-of-care for patient treatment decisions. We evaluated genotype concordance between tumor DNA and genomic DNA from blood and catalogued functional effects of somatic mutations in 21 drug response genes in 752 solid tumor patients. Using a threshold of 10% difference between tumor and blood DNA variant allele fraction (VAF), concordance for heterogenous genotype calls was 78% and increased to 97.5% using a 30% VAF threshold. Somatic mutations were observed in all 21 drug response genes, and 44% of patients had at least one somatic mutation in these genes. In tumor DNA, eight patients had a frameshift mutation in CYP2C8, which metabolizes taxanes. Overall, somatic copy number losses were more frequent than gains, including for CYP2C19 and CYP2D6 which had the most frequent copy number losses. However, copy number gains in TPMT were more than four times as common as losses. Seven % of patients had copy number gains in ABCB1, a multidrug resistance transporter of anti-cancer agents. These results demonstrate tumor-only DNA sequencing might not be reliable to call germline genotypes of drug response variants.

PMID:36709390 | DOI:10.1038/s41397-023-00299-7

Eur J Clin Pharmacol. 2023 Jan 28. doi: 10.1007/s00228-023-03458-8. Online ahead of print.

ABSTRACT

BACKGROUND: The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking.

AIM: We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients.

METHOD: Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events.

RESULTS: Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke.

CONCLUSION: Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

PMID:36708395 | DOI:10.1007/s00228-023-03458-8

Nat Rev Genet. 2023 Jan 27. doi: 10.1038/s41576-022-00572-8. Online ahead of print.

ABSTRACT

Inter-individual variability in drug response, be it efficacy or safety, is common and likely to become an increasing problem globally given the growing elderly population requiring treatment. Reasons for this inter-individual variability include genomic factors, an area of study called pharmacogenomics. With genotyping technologies now widely available and decreasing in cost, implementing pharmacogenomics into clinical practice - widely regarded as one of the initial steps in mainstreaming genomic medicine - is currently a focus in many countries worldwide. However, major challenges of implementation lie at the point of delivery into health-care systems, including the modification of current clinical pathways coupled with a massive knowledge gap in pharmacogenomics in the health-care workforce. Pharmacogenomics can also be used in a broader sense for drug discovery and development, with increasing evidence suggesting that genomically defined targets have an increased success rate during clinical development.

PMID:36707729 | DOI:10.1038/s41576-022-00572-8

Paediatr Drugs. 2023 Jan 27. doi: 10.1007/s40272-023-00560-3. Online ahead of print.

ABSTRACT

As the activity of certain drug metabolizing enzymes or transporter proteins can vary with age, the effect of ontogenetic and genetic variation on the activity of these enzymes is critical for the accurate prediction of treatment outcomes and toxicity in children. This makes pharmacogenetic research in pediatrics particularly important and urgently needed, but also challenging. This review summarizes pharmacogenetic studies on the effects of genetic polymorphisms on pharmacokinetic parameters and clinical outcomes in pediatric populations for certain drugs, which are commonly prescribed by clinicians across multiple therapeutic areas in a general hospital, organized from those with the most to the least pediatric evidence among each drug category. We also further discuss the research status of the gene-guided dosing regimens and clinical implementation of pediatric pharmacogenetics. More and more drug-gene interactions are demonstrated to have clinical validity for children, and pharmacogenomics in pediatrics have shown evidence-based benefits to enhance the efficacy and precision of existing drug dosing regimens in several therapeutic areas. However, the most important limitation to the implementation is the lack of high-quality, rigorous pediatric prospective clinical studies, so adequately powered interventional clinical trials that support incorporation of pharmacogenetics into the care of children are still needed.

PMID:36707496 | DOI:10.1007/s40272-023-00560-3

Eur Neuropsychopharmacol. 2023 Jan 25;69:26-46. doi: 10.1016/j.euroneuro.2023.01.001. Online ahead of print.

ABSTRACT

To study mental illness and health, in the past researchers have often broken down their complexity into individual subsystems (e.g., genomics, transcriptomics, proteomics, clinical data) and explored the components independently. Technological advancements and decreasing costs of high throughput sequencing has led to an unprecedented increase in data generation. Furthermore, over the years it has become increasingly clear that these subsystems do not act in isolation but instead interact with each other to drive mental illness and health. Consequently, individual subsystems are now analysed jointly to promote a holistic understanding of the underlying biological complexity of health and disease. Complementing the increasing data availability, current research is geared towards developing novel methods that can efficiently combine the information rich multi-omics data to discover biologically meaningful biomarkers for diagnosis, treatment, and prognosis. However, clinical translation of the research is still challenging. In this review, we summarise conventional and state-of-the-art statistical and machine learning approaches for discovery of biomarker, diagnosis, as well as outcome and treatment response prediction through integrating multi-omics and clinical data. In addition, we describe the role of biological model systems and in silico multi-omics model designs in clinical translation of psychiatric research from bench to bedside. Finally, we discuss the current challenges and explore the application of multi-omics integration in future psychiatric research. The review provides a structured overview and latest updates in the field of multi-omics in psychiatry.

PMID:36706689 | DOI:10.1016/j.euroneuro.2023.01.001