From nutrigenomics to personalizing diets: are we ready for precision medicine?
Ontology highlight
ABSTRACT:
SUBMITTER: Loos RJF
PROVIDER: S-EPMC6358032 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
Publications
From nutrigenomics to personalizing diets: are we ready for precision medicine?
The American journal of clinical nutrition 20190101 1
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Project description:The modern food system feeds six billion people with remarkable diversity, safety, and nutrition. Yet, the current rise in diet-related diseases is compromising health and devaluing many aspects of modern agriculture. Steps to increase the nutritional quality of individual foods will assist in personalizing health and in guiding individuals to achieve superior health. Nutrigenomics is the scientific field of the genetic basis for varying susceptibilities to disease and the diverse responses to foods. Although some of these genetic determinants will be simple and amenable to personal genotyping as the means to predict health, in practice most will not. As a result, genotyping will not be the secret to personalizing diet and health. Human assessment technologies from imaging to proteomics and metabolomics are providing tools to both understand and accurately assess the nutritional phenotype of individuals. The business models are also emerging to bring these assessment capabilities to industrial practice, in which consumers will know more about their personal health and seek personal solutions.
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Project description:As one of the key tools on the precision medicine workbench, high-throughput genetic testing has enormous promise for improving healthcare outcomes. Tunisia has made tremendous progress in acquiring and implementing the technology in the clinical context. However, current utilization does not ensure the whole range of benefits that high-throughput genomic testing provides which impedes the country's ability to move forward into the new era of precision medicine. This issue is primarily related to the current state of Tunisia's healthcare ecosystem and the sociological attributes of its population, creating numerous challenges that must be addressed. In the current review, we aimed to identify and highlight these challenges that may be prevalent in other low and middle-income countries. Essentially, they fall into three main categories that include the socio-economic landscape in Tunisia, which prevents citizens from engaging in precision medicine activities; the current settings of the healthcare system that lack or miss key components for the successful implementation of precision medicine practices; and the inability of the current infrastructure and resources to handle the various challenges related to genomic data and metadata. We also propose five pillar solutions as a framework for addressing all of these challenges, which could strengthen Tunisia's capability for effective precision medicine implementation in today's clinical environment.
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| S-EPMC9531153 | biostudies-literature
Project description:Rapid advances in technology and data science have the potential to improve the precision of preventive and therapeutic interventions, and enable the right treatment to be recommended, at the right time, to the right person. There are well-described examples of successful precision medicine approaches for monogenic conditions such as specific diets for phenylketonuria, and sulfonylurea treatments for certain types of MODY. However, the majority of chronic diseases are polygenic, and it is unlikely that the research strategies used for monogenic diseases will deliver similar changes to practice for polygenic traits. Type 2 diabetes, for example, is a multifactorial, heterogeneous, polygenic palette of metabolic disorders. In this non-systematic review I highlight limitations of the evidence, and the challenges that need to be overcome prior to implementation of precision medicine in the prevention and management of type 2 diabetes. Most precision medicine approaches are spuriously precise, overly complex and too narrowly focused on predicting blood glucose levels with a limited set of characteristics of individuals rather than the whole person and their context. Overall, the evidence to date is insufficient to justify widespread implementation of precision medicine approaches into routine clinical practice for type 2 diabetes. We need to retain a degree of humility and healthy scepticism when evaluating novel strategies, and to demand that existing evidence thresholds are exceeded prior to implementation.
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Project description:Sickle cell disease (SCD) is a blood disease caused by a single nucleotide substitution (T > A) in the beta globin gene on chromosome 11. The single point mutation (Glu6Val) promotes polymerization of hemoglobin S (HbS) and causes sickling of erythrocytes. Vaso-occlusive painful crises are associated with recurrent and long-term use of analgesics/opioids and hydroxyurea (HU) by people living with SCD. The present analysis offers a state-of-the-art expert review of the effectiveness of pharmacogenomics/genetics of pain management in SCD, with specific focus on HU and opioids. The literature search used the following keywords: SCD, pharmacogenomics, pharmacogenetics, pain, antalgics, opioids, morphine, and HU. The literature was scanned until March 2016, with specific inclusion of targeted landmark and background articles on SCD. Surprisingly, our review identified only a limited number of studies that addressed the genetic/genomic basis of variable responses to pain (e.g., variants in OPRM1, HMOX-1, GCH1, VEGFA COMT genes), and pharmacogenomics of antalgics and opioids (e.g., variants in OPRM1, STAT6, ABCB1, and COMT genes) in SCD. There has been greater progress made toward identifying the key genomic variants, mainly in BCL11A, HBS1L-MYB, or SAR1, which contribute to response to HU treatment. However, the complete picture on pharmacogenomic determinants of the above therapeutic phenotypes remains elusive. Strikingly, no study has been conducted in sub-Saharan Africa where majority of the patients with SCD live. This alerts the broader global life sciences community toward the existing disparities in optimal and ethical targeting of research and innovation investments for SCD specifically and precision medicine and pharmacology research broadly.
| S-EPMC5067801 | biostudies-literature
Project description:Personalized medicine has been identified as a powerful tool for addressing the myriad of health issues facing different health systems globally. Although recent studies have expanded our understanding of how different factors such as genetics and the environment play significant roles in affecting the health of individuals, there are still several other issues affecting their translation into personalizing health interventions globally. Since African populations have demonstrated huge genetic diversity, there is a significant need to apply the concepts of personalized medicine to overcome various African-specific health challenges. Thus, we review the current state, progress, and challenges facing the adoption of personalized medicine in Africa with a view to providing insights to critical stakeholders on the right approach to deploy.
| S-EPMC10546210 | biostudies-literature
Project description:Project Description
Esophagitis is a frequent, but at the molecular level poorly characterized condition with diverse underlying etiologies and treatments. Correct diagnosis can be challenging due to partially overlapping histological features. By proteomic profiling of 55 biopsy specimens representing controls, Reflux- (GERD), Eosinophilic-(EoE), Crohns-(CD), and Herpes simplex (HSV)-esophagitis, as well as Candida albicans infection by LC-MS/MS, we identified distinct signatures and functional networks. Our integrated AI-assisted morphoproteomic approach allows deeper insights in disease-specific molecular alterations and represents a promising tool in esophagitis-related precision medicine.
The FFPE samples were further processed including macrodissection, protein extraction, protein precipitation, protein digestion, and peptide clean up according to a previously published and modified protocol (Buczak et al., 2020). For further details, please refer to the Materials and Methods section of the manuscript.
In depth proteomic characterization of the samples a label free high-resolution LC-MS/MS approach using an Orbitrap Tribrid Fusion mass spectrometer was chosen (operated in DIA mode). Tryptic peptides were loaded onto a µPAC Trapping Column with a pillar diameter of 5 µm, inter-pillar distance of 2.5 µm, pillar length/bed depth of 18 µm, external porosity of 9%, bed channel width of 2 mm and length of 10 mm; pillars are superficially porous with a porous shell thickness of 300 nm and pore sizes in the order of 100 to 200 Å at a flow rate of 10 µl per min in 0.1% trifluoroacetic acid in HPLC-grade water. Peptides were eluted and separated on the PharmaFluidics µPAC nano-LC column: 50 cm µPAC C18 with a pillar diameter of 5 µm, inter-pillar distance of 2.5 µm, pillar length/bed depth of 18 µm, external porosity of 59%, bed channel width of 315 µm and bed length of 50 cm; pillars are superficially porous with a porous shell thickness of 300 nm and pore sizes in the order of 100 to 200 Å by a linear gradient from 2% to 30 % of buffer B (80% acetonitrile and 0.08% formic acid in HPLC-grade water) in buffer A (2% acetonitrile and 0.1% formic acid in HPLC-grade water) at a flow rate of 300 nl per min. The remaining peptides were eluted by a short gradient of 10 minutes from 30% to 95% buffer B; followed by 25 minutes at 2% of buffer B, the total gradient run was 120 min.
Spectra were acquired in DIA mode using 50 variable-width windows over the mass range 350-1500 m/z. The Orbitrap was used for MS1 and MS2 detection, with an AGC target for MS1 set to 20x104 and a maximum injection time to 100 ms. MS2 scan range was set between 200 and 2000 m/z, with a minimum of 6 points across the peak. Orbitrap resolution for MS2 was set to 30K, isolation window set to 1.6, AGC target to 50x104 and maximum injection time to 54 ms. MS1 and MS2 data were acquired in centroid mode.
In order to check for retention time (RT) stability, iRT standards (Biognosys) were spiked in each sample according to the manufacturer recommendations, the 11 iRT peptide sequences were manually added to the database and used during DIA-NN search to generate the precursor ion library used for MS data analysis. To reduce the possibility of carry over and cross contamination between the samples, two BSA washes were used between samples, and a trap column wash followed by 2 BSA washes was used every 10 samples sequence.
The above-mentioned workflow is schematically displayed in Fig. 1B.
LC-MS/MS was performed at the Proteome Center Tuebingen (PCT). Here, 250 ng of peptides were loaded onto an Easy-nLC 1200 system coupled to a quadrupole Orbitrap Exploris 480 mass spectrometer (all Thermo Fisher Scientific, Waltham, MA, USA) as previously described (Krauss et al, 2023).
MS raw data files were analyzed using DIA-NN 1.8.1 (Demichev et al, 2020) in library-free mode against the human database (UniProt release March 2024, 20412 proteins). First, a precursor ion library was generated using FASTA digest for library-free search in combination with deep learning-based spectra prediction. An experimental library generated from the DIA-NN search was used for cross-run normalization and mass accuracy correction. Only high-accuracy spectra with a minimum precursor FDR of 0.01, and only tryptic peptides (2 missed Tryptic cleavages) were used for protein quantification. The match between runs option was activated and no shared spectra were used for protein identification. Similarly, Normal, HSV, and Candida samples were searched against reviewed entries of HSV1 (taxonomy id 10298, 125 entries), HSV2 (taxonomy id 10310, 95 entries), and C. albicans (taxonomy id 5476, 1412 entries) downloaded on 04.03.2024, in addition to the human database.
2024-06-10 | MSV000094966 | MassIVE
Project description:Colorectal cancers are the leading cancers for both sexes combined. They represent 15-20% of all cancers. This cancer has a severe prognosis, the survival rate at 5 years is around 55% and in France it is estimated, all colorectal cancers are responsible for an annual mortality of 15,000 patients. The prognosis of colon cancer knows no significant improvement.
The treatment of colon cancer is surgical. It is intended for removal of colonic segment bearing the tumor with margins of healthy colon. The therapeutic attitude following the surgery is essentially driven by histopathology of the tumor. Adjuvant chemotherapy for all patients with localized stage II provides no benefit because the effectiveness of chemotherapy is limited and vulnerable to systemic toxicity. However, nearly 30% of patients with stage II disease will have a recurrence / metastasis. These patients could benefit from adjuvant chemotherapy.
Intense research efforts have been made to identify markers predictive of relapse. Over thirty biological markers (eg. Mutations, deletions, chromosomal instability, ...) were highlighted. None of them has so far sufficient prognostic value (independent of TNM) to justify routine application in clinical practice in order to adapt the treatment of patients.
The identification of new prognostic markers is a major issue for colorectal cancer. We showed that the intratumoral density memory T lymphocytes (CD45RO) and cytotoxic (CD8) strongly influenced the clinical outcome of patients. We have developed and validated a "immunoscore" technique intratumoral immune quantification and creates a platform to facilitate the clinical immuno transfer.
We are currently conducting a large international retrospective study (22 centers,> 9000 patients) with promotion of cancer immunotherapy Company (SITC) to validate the method "immunoscore." At the same time, we are conducting a prospective multicenter study "ImmuCol" (National PHRC) to validate the prognostic value of "immunoscore" in colorectal cancer stage I-IV. The goal of inclusion has been achieved, as 420 patients were included for 18 months. Clinical follow-up will be 3 years after surgery.
The program ImmuCol2 research takes advantage of the ImmuCol study to extend the investigation beyond the immunoscore to define the combination of interest, prognostic and theranostic parameters at diagnosis and during the clinical course patients with an objective of personalized medicine.
| 2177040 | ecrin-mdr-crc
Project description:The relationship between nutrition and genes has long been hinted at and sometimes plainly associated with certain diseases. Now, after many years of research and coincidental findings, it is believed that this relationship, termed "Nutrigenomics," is certainly a factor of major importance in various conditions. In this review article, we discuss nutrigenomics, starting with basics definitions and enzymatic functions and ending with its palpable association with cancer. Now, diet is basically what we eat on a daily basis. Everything that enters through our alimentary tract ends up broken down to minute molecules and amino acids. These molecules interact with our microbiome and genome in discreet ways. For instance, we demonstrate how proper intake of probiotics enhances beneficial bacteria and may alleviate IBS and prevent colorectal cancer on the long term. We also show how a diet rich in folic acid is essential for methylenetetrahydrofolate reductase (MTHFR) function, which lowers risk of colorectal cancer. Also, we discuss how certain diets were associated with development of certain cancers. For example, red and processed meat are highly associated with colorectal and prostate cancer, salty diets with stomach cancer, and obesity with breast cancer. The modification of these diets significantly lowered the risk and improved prognosis of these cancers among many others. We also examined how micronutrients had a role in cancer prevention, as vitamin A and C exert anti-carcinogenic effects through their function as antioxidants. In addition, we show how folic acid prevent DNA mutations by enhancing protein methylation processes. Finally, after a systematic review of myriad articles on the etiology and prevention of cancer, we think that diet should be a crucial feature in cancer prevention and treatment programs. In the future, healthy diets and micronutrients may even be able to successively alter the liability to genetic mutations that result in cancer. It also will play a role in boosting treatment and improving prognosis of diagnosed cancers.
| S-EPMC10665279 | biostudies-literature
Project description:The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed), an initiative of five Research Innovation and Dissemination Centers (RIDCs) supported by FAPESP.
2020-08-22 | GSE156652 | GEO