Advancing precision medicine with personalized drug screening

2021

Genomic medicine has created a great deal of hope since the completion of the Human Genome Project (HGP). Genomic medicine promises disease prevention and early diagnosis in the context of precision medicine. Precision medicine as a scientific discipline has introduced as an evolution in medicine. The rapid growth of high-development technologies permits the assessment of biological systems. Study of the integrated profiles of omics, such as genome, transcriptome, proteome and other omics information lead to significant advances in personalized and precision medicine. In the context of precision medicine, pharmacogenomics can play an important role in order to discriminate responders and non-responders to medications and avoiding toxicity and achieving the optimum dose. So precision medicine in accordance with genomic medicine will transform medicine from conventional evidence-based medicine in the diagnosis and treatment towards precision based-medicine. In this review, we have sum...

Omics for Personalized Medicine, 2013

Adverse drug reactions (ADRs) are one of the most dreadful medical conditions that affect a considerable number of individuals when they are taking single or multiple prescription drugs. Often these adverse reactions can occur with specialized drugs that are used to treat more serious disorders. Seldom ADRs can also occur due to intake of even simpler drugs such as penicillin and aspirin. In spite of volumes of data on ADRs, at present we still go through "one size fi ts all" model in dealing with prescription drugs. This scenario could change due to the emergence of new ways to overcome or minimize ADRs. Pharmacogenomics is one such ways to overcome many horrors of side effects caused by drugs, including ADRs. Pharmacogenomics is the combination of pharmacy and the patient's genetic composition which interact in an intricate manner to produce positive as well as negative drug reactions. When positive, it is for the betterment of patients, and when negative it leads to ADRs which oftentimes is fatal. Pharmacogenomics is an emerging fi eld of science which is still in its infancy. Technologies that were developed along with the Human Genome Project (HGP), such as faster DNA sequencing protocols and effi cient data handling softwares would help in the rapid advancement of pharmacogenomics in the near future. In addition, the reduced cost to obtain complete sequence of individual genome would provide data on single nucleotide polymorphisms (SNPs) and haplotype map (HapMap). These data would provide pattern of individual genetic variations which could be useful in managing diseases and treating patients effectively. In this chapter we will look at the current status and the future of pharmacogenomics which will aid in the development of personalised care. We will also discuss some of the obstacles that would have to be dealt with in achieving such target.

Molecular Systems Biology, 2014

Inferring potential drug indications, for either novel or approved drugs, is a key step in drug development. Previous computational methods in this domain have focused on either drug repositioning or matching drug and disease gene expression profiles. Here, we present a novel method for the large-scale prediction of drug indications (PREDICT) that can handle both approved drugs and novel molecules. Our method is based on the observation that similar drugs are indicated for similar diseases, and utilizes multiple drug-drug and disease-disease similarity measures for the prediction task. On cross-validation, it obtains high specificity and sensitivity (AUC¼0.9) in predicting drug indications, surpassing existing methods. We validate our predictions by their overlap with drug indications that are currently under clinical trials, and by their agreement with tissue-specific expression information on the drug targets. We further show that diseasespecific genetic signatures can be used to accurately predict drug indications for new diseases (AUC¼0.92). This lays the computational foundation for future personalized drug treatments, where gene expression signatures from individual patients would replace the disease-specific signatures. Molecular Systems Biology 7:496;

Expert Review of Molecular Diagnostics, 2007

Bio-Algorithms and Med-Systems

Along with the development of modern science, medical knowledge and therapy become more and more precise and personal as a consequence. Genetics and immunology participate in the progress in particular. They open the way to molecular knowledge, allowing precise interpretation of pathology in individual cases followed by finding proper therapy. However, the large-scale improvement of medical efficacy seems to be achieved with the development of screening tests that, being not invasive and cheap, may allow for personal repeatable use and early revealing of threatening diseases.

Pharmacogenomics, 2019

The Fourth European Society of Pharmacogenomics and Personalized Therapy biennial conference was organized in collaboration with the Italian Society of Personalized Medicine (SIMeP) and was held at Benedictine Monastery of San Nicolò l’Arena in Catania, Sicily (Italy) on 4–7 October 2017. The congress addressed the research progress and clinical implementation in pharmacogenomics and personalized medicine. The Fourth European Society of Pharmacogenomics and Personalized Therapy congress brought together leading international scientists and healthcare professionals actively working in the fields of pharmacogenomics and personalized therapy. Altogether, 25 speakers in 15 session comprehensively covered broad spectrum of pharmacogenetics and pharmacogenomics research, clinical applications in different clinical disciplines attended by 270 delegates.

Clinical Chemistry, 2013

BACKGROUND The practice of personalized medicine has made large strides since the introduction of high-throughput technologies and the vast improvements in computational biotechnology. The personalized-medicine approach to cancer management holds promise for earlier disease detection, accurate prediction of prognosis, and better treatment options; however, the early experience with personalized medicine has revealed important concerns that need to be addressed before research findings can be translated to the bedside. CONTENT We discuss several emerging “practical” or “focused” applications of personalized medicine. Molecular testing can have an important positive impact on health and disease management in a number of ways, and the list of specific applications is evolving. This list includes improvements in risk assessment, disease prevention, identification of new disease-related mutations, accurate disease classification based on molecular signatures, selection of patients for en...

Personalized Medicine, 2014

As the past decade featured significant discoveries in the field of pharmacogenomics and genomics research, the next decade will be likely characterized by measures and policies to maximally exploit these scientific discoveries to the benefit of the patients and societies in all parts of the world. " part of

Nature Reviews Drug Discovery, 2006

| The success of the Human Genome Project raised expectations that the knowledge gained would lead to improved insight into human health and disease, identification of new drug targets and, eventually, a breakthrough in healthcare management. However, the realization of these expectations has been hampered by the lack of essential data on genotype-drug-response phenotype associations. We therefore propose a follow-up to the Human Genome Project: forming global consortia devoted to archiving and analysing group and individual patient data on associations between genotypes and drug-response phenotypes. Here, we discuss the rationale for such personalized medicine databases, and the key practical and ethical issues that need to be addressed in their establishment.

Rapid Communications in Mass Spectrometry, 2020

Rationale: Advances in metabolomics, together with consolidated genetic approaches, have opened the way for investigating the health of patients using a large number of molecules simultaneously, thus providing firm scientific evidence for personalized medicine and consequent interventions. Metabolomics is an ideal approach for investigating specific biochemical alterations occurring in rare clinical situations, such as those caused by rare associations between comorbidities and immunosuppression. Methods: Metabolomic database matching enables clear identification of molecular factors associated with a metabolic disorder, and can provide a rationale for elaborating personalized therapeutic protocols. Mass spectrometry forms the basis of metabolomics and uses mass-to-charge ratios for metabolite identification. Here, we used a mass spectrometry-based approach to diagnose and develop treatment options in the clinical case of a patient afflicted with a rare disease further complicated by immunosuppression. The patient's data were analyzed using proprietary databases, and a personalized and efficient therapeutic protocol was consequently elaborated. Results: The patient displayed significant alterations in homocysteine:methionine and homocysteine:thiodiglycol acid plasma concentration ratios and these were associated with low immune system function. This led to cysteine concentration deficiency causing extreme oxidative stress. Plasmatic thioglycolic acid concentrations were initially altered and were used for therapeutic follow-up and to evaluate cysteine levels. Conclusions: A mass spectrometry-based pharmacometabolomic approach was used to define a personalized protocol in a clinical case of rare peritoneal carcinosis with confounding immunosuppression. This personalized protocol reduced both oxidative stress and resistance to antibiotics and antiviral drugs.