skip to main content
US FlagAn official website of the United States government
dot gov icon
Official websites use .gov
A .gov website belongs to an official government organization in the United States.
https lock icon
Secure .gov websites use HTTPS
A lock ( lock ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.


Title: The Existence of at Least Three Genomic Signature Patterns and at Least Seven Subtypes of COVID-19 and the End of the Disease
Hoping to find genomic clues linked to COVID-19 and end the pandemic has driven scientists’ tremendous efforts to try all kinds of research. Signs of progress have been achieved but are still limited. This paper intends to prove the existence of at least three genomic signature patterns and at least seven subtypes of COVID-19 driven by five critical genes (the smallest subset of genes) using three blood-sampled datasets. These signatures and subtypes provide crucial genomic information in COVID-19 diagnosis (including ICU patients), research focuses, and treatment methods. Unlike existing approaches focused on gene fold-changes and pathways, gene-gene nonlinear and competing interactions are the driving forces in finding the signature patterns and subtypes. Furthermore, the method leads to high accuracy with hospitalized patients, showing biological and mathematical equivalences between COVID-19 status and the signature patterns and a methodological advantage over other methods that cannot lead to high accuracy. As a result, as new biomarkers, the new findings and genomic clues can be much more informative than other findings for interpreting biological mechanisms, developing the second (third) generation of vaccines, antiviral drugs, and treatment methods, and eventually bringing new hopes of an end to the pandemic.  more » « less
Award ID(s):
2012298
PAR ID:
10340959
Author(s) / Creator(s):
Date Published:
Journal Name:
Vaccines
Volume:
10
Issue:
5
ISSN:
2076-393X
Page Range / eLocation ID:
761
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Known genes in the breast cancer study literature could not be confirmed whether they are vital to breast cancer formations due to lack of convincing accuracy, although they may be biologically directly related to breast cancer based on present biological knowledge. It is hoped vital genes can be identified with the highest possible accuracy, for example, 100% accuracy and convincing causal patterns beyond what has been known in breast cancer. One hope is that finding gene-gene interaction signatures and functional effects may solve the puzzle. This research uses a recently developed competing linear factor analysis method in differentially expressed gene detection to advance the study of breast cancer formation. Surprisingly, 3 genes are detected to be differentially expressed in TNBC and non-TNBC (Her2, Luminal A, Luminal B) samples with 100% sensitivity and 100% specificity in 1 study of triple-negative breast cancers (TNBC, with 54 675 genes and 265 samples). These 3 genes show a clear signature pattern of how TNBC patients can be grouped. For another TNBC study (with 54 673 genes and 66 samples), 4 genes bring the same accuracy of 100% sensitivity and 100% specificity. Four genes are found to have the same accuracy of 100% sensitivity and 100% specificity in 1 breast cancer study (with 54 675 genes and 121 samples), and the same 4 genes bring an accuracy of 100% sensitivity and 96.5% specificity in the fourth breast cancer study (with 60 483 genes and 1217 samples). These results show the 4-gene-based classifiers are robust and accurate. The detected genes naturally classify patients into subtypes, for example, 7 subtypes. These findings demonstrate the clearest gene-gene interaction patterns and functional effects with the smallest numbers of genes and the highest accuracy compared with findings reported in the literature. The 4 genes are considered to be essential for breast cancer studies and practice. They can provide focused, targeted researches and precision medicine for each subtype of breast cancer. New breast cancer disease types may be detected using the classified subtypes, and hence new effective therapies can be developed. 
    more » « less
  2. There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer. 
    more » « less
  3. null (Ed.)
    The new coronavirus (now named SARS-CoV-2) causing the disease pandemic in 2019 (COVID-19), has so far infected over 35 million people worldwide and killed more than 1 million. Most people with COVID-19 have no symptoms or only mild symptoms. But some become seriously ill and need hospitalization. The sickest are admitted to an Intensive Care Unit (ICU) and may need mechanical ventilation to help them breath. Being able to predict which patients with COVID-19 will become severely ill could help hospitals around the world manage the huge influx of patients caused by the pandemic and save lives. Now, Hao, Sotudian, Wang, Xu et al. show that computer models using artificial intelligence technology can help predict which COVID-19 patients will be hospitalized, admitted to the ICU, or need mechanical ventilation. Using data of 2,566 COVID-19 patients from five Massachusetts hospitals, Hao et al. created three separate models that can predict hospitalization, ICU admission, and the need for mechanical ventilation with more than 86% accuracy, based on patient characteristics, clinical symptoms, laboratory results and chest x-rays. Hao et al. found that the patients’ vital signs, age, obesity, difficulty breathing, and underlying diseases like diabetes, were the strongest predictors of the need for hospitalization. Being male, having diabetes, cloudy chest x-rays, and certain laboratory results were the most important risk factors for intensive care treatment and mechanical ventilation. Laboratory results suggesting tissue damage, severe inflammation or oxygen deprivation in the body's tissues were important warning signs of severe disease. The results provide a more detailed picture of the patients who are likely to suffer from severe forms of COVID-19. Using the predictive models may help physicians identify patients who appear okay but need closer monitoring and more aggressive treatment. The models may also help policy makers decide who needs workplace accommodations such as being allowed to work from home, which individuals may benefit from more frequent testing, and who should be prioritized for vaccination when a vaccine becomes available. 
    more » « less
  4. Abstract Objective Through the coronavirus disease 2019 (COVID-19) pandemic, telemedicine became a necessary entry point into the process of diagnosis, triage and treatment. Racial and ethnic disparities in health care have been well documented in COVID-19 with respect to risk of infection and in-hospital outcomes once admitted, and here we assess disparities in those who access healthcare via telemedicine for COVID-19 . Materials and Methods Electronic health record data of patients at New York University Langone Health between March 19th and April 30, 2020 were used to conduct descriptive and multilevel regression analyses with respect to visit type (telemedicine or in-person), suspected COVID diagnosis and COVID test results. Results Controlling for individual and community-level attributes, Black patients had 0.6 times the adjusted odds (95%CI:0.58-0.63) of accessing care through telemedicine compared to white patients, though they are increasingly accessing telemedicine for urgent care, driven by a younger and female population. COVID diagnoses were significantly more likely for Black versus white telemedicine patients. Discussion There are disparities for Black patients accessing telemedicine, however increased uptake by young, female Black patients. Mean income and decreased mean household size of Zip code were also significantly related to telemedicine use. Conclusion Telemedicine access disparities reflect those in in-person healthcare access. Roots of disparate use are complex and reflect individual, community, and structural factors, including their intersection; many of which are due to systemic racism. Evidence regarding disparities that manifest through telemedicine can be used to inform tool design and systemic efforts to promote digital health equity. 
    more » « less
  5. Due to the essential role of dentists in stopping the COVID-19 pandemic, the purpose of this review is to help dentists to detect any weaknesses in their disinfection and cross-contamination prevention protocols, and to triage dental treatments to meet the needs of patients during the pandemic. We used PRISMA to identify peer-reviewed publications which supplemented guidance from the center for disease control about infection control and guidelines for dentists. Dentists must triage dental treatments to meet the needs of patients during the pandemic. The ongoing pandemic has changed the practice of dentistry forever, the changes make it more cumbersome, time-consuming, and costly due to the possible pathways of transmission and mitigation steps needed to prevent the spread of COVID-19. Dental chairside rapid tests for SARS-CoV-2 are urgently needed. Until then, dentists need to screen patients for COVID-19 even though 75% of people with COVID-19 have no symptoms. Despite the widespread anxiety and fear of the devastating health effects of COVID-19, only 61% of dentists have implemented a change to their treatment protocols. As an urgent matter of public health, all dentists must identify the additional steps they can take to prevent the spread of COVID-19. The most effective steps to stop the pandemic in dental offices are to; vaccinate all dentists, staff, and patients; triage dental treatments for patients, separate vulnerable patients, separate COVID-19 patients, prevent cross-contamination, disinfect areas touched by patients, maintain social distancing, and change personal protective equipment between patients. 
    more » « less