Copy of Integrated Genetic Sequencing and Multi-omics Approaches to Investigate Taste Disorder Associated with Diabetes and COVID-19
Introduction
The sense of taste is closely related to our health, particularly evident when we develop symptoms of certain diseases. A common example is that when we catch a cold, not only will our noses become clogged, but also will we suffer from reduced sense of taste. Another example would be that around 50% of people with COVID-19 report a change in their sense of taste or smell1.
With the technological advancements in next generation sequencing and genomics applications in recent years, as well as the vast array of open-source genomic databases, innovative research into the connection between human taste and various disease states is becoming more prevalent.
Genetic Analysis of Taste Receptors in Blood Sugar Regulation and Diabetes
Our taste receptors, generally known as taste buds, are mainly found on our tongues but also in the roof of our mouths and throats. The taste buds respond to various stimuli and help to prepare our body to metabolize food once it is ingested. They also enable us to evaluate food for the presence of nutrients or even toxins. For example, we perceive the taste of many compounds that are toxic to the human body to be bitter2. Taste receptor genes are increasingly being explored for their links with certain metabolic conditions such as Type 2 Diabetes Mellitus (T2DM).
A recent study by Lee and Shin utilised data sourced from the Korean Genome and Epidemiology Study (KoGES) and genotype data from the Korea Biobank Arrary (KoreanChip) containing 833,535 SNPs3. The data attained using advanced Illumina platform were aligned to GRCh37 using Burrows-Wheeler Aligner (BWA) at default settings4. The TAS2R4 rs2233998 genotype was investigated in this study, as out of the 74 SNPs reported within the TAS2R4 (taste 2 receptor member 4) family. The genomic data, combined with dietary assessment of study participants via validated semi-quantitative food frequency questionnaires, demonstrated significant associations between the TAS2R4 rs2233998 genotype and the incidence of T2DM among women.
Tanycytes are a specific type of glial cell which are located in the median eminence (ME) at the base of the brain responsible for controlling the body’s internal balance, i.e.: homeostasis. A recent study by Yu et al examined a particular subset of these cells, called M5 tanycytes, which express genes associated with taste transduction, including bitter taste receptors. Due to the close proximity of M5 tanycytes to the ME, the researchers posited that the cells could contribute to the control of energy metabolism by mediating communication between the blood, the cerebrospinal fluid, and neighbouring hypothalamic areas.
They tested whether the cells could adapt to extreme metabolic conditions such as fasting by isolating the specific cell populations from fasted mice via Fluorescence-Associated Cell Sorting (FACS), followed by RNA sequencing (RNA-seq) provided by Novogene. They demonstrated that activating M5 tanycytes leads to the secretion of insulin, and conversely showed that when these cells are inactivated, mice with diet-induced obesity showed impaired glucose tolerance. This research provides interesting insight into the complex interlinking between taste receptors and glucose regulation and homeostasis, and further research on these cells in the context of diabetes is warranted5.
The Involvement of Oral Cavity in COVID-19 Pathogenesis
SARS-CoV-2 is the virus that causes COVID-19, characterised by the WHO as an airborne virus transmitted by asymptomatic, pre-symptomatic and symptomatic individuals via exposure to infected droplets and aerosols. As previously mentioned, about half of the cases present oral manifestations of COVID-19, such as loss of taste, dry mouth, and oral lesions.
Research carried out by Huang et al aimed to address a gap in knowledge about whether SARS-CoV-2 can directly infect and replicate in oral tissues such as salivary glands (SGs) or mucosa. Blood samples were collected from individuals suffering from severe COVID-19, as well as healthy individuals as a control group and all contributors were either positively or negatively confirmed by SARS-CoV-2 nucleic acid RT-qPCR testing. A multi-omics approach was used to analyse the metabolome of the COVID-19 cohort to navigate the complex landscape of the proteome and metabolome profiles through intuitive visual analytics6.
This study was the first of its kind to explore the distinctions between single omics and multi-omics analyses in COVID-19 research. In order to confirm the advantages of multi-omics approaches over traditional single omics analysis, untargeted proteomics and metabolomics techniques were utilised to examine the plasma proteins and metabolites in a group of 32 COVID-19 patients with severe symptoms.
The researchers aimed to analyse these profiles to illustrate the molecular landscape uncovered by each analysis method. They found that integrating knowledge-based and statistical-based techniques outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. This study not only provided insight into COVID-19 infection, but also provided a platform that could give us a better understanding of the molecular mechanisms behind biological systems and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor6.
The multi-omics approach used in this study revealed the involvement of the complement system in COVID-19 pathogenesis, suggesting that the suppression of this system could benefit severe COVID-19 patients. This approach also helped to identify a range of acute-phase proteins in platelet activation, signalling, and aggregation, along with unique functional proteins, while the single omics approach reported fewer proteins in this pathway.
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Finally, the study highlighted the role of purine metabolism, signalling and transport pathways in the immune response to tissue injuries and cell damage in COVID-19, suggesting that purine metabolism plays an important role in immune regulation and anti-inflammation processes in severe infection6.
Conclusion
As highlighted in this article, in relation to disease pathogenesis in the context of human taste, integrated genetic sequencing and multi-omics technologies are powerful tools that can provide a comprehensive and detailed insight into the underpinnings of disease pathogenesis. Advancement in this area is expected to revolutionize disease research by enabling more accurate diagnoses, targeted therapies, and a deeper understanding of disease mechanisms and outcomes, ultimately improving patient outcomes.
Building on years of sequencing expertise and efficient standard workflow, Novogene offers versatile solutions for multiple biological inquiries, spanning genomics, transcriptomics, epigenomics, and metagenomics. Click here for more details about our services: https://www.novogene.com/services/research-services
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