MOATAI-VIR - an AI algorithm that predicts severe adverse events and molecular features for COVID-19’s complications

AbstractFollowing SARS-CoV-2 infection, some COVID-19 patients experience severe adverse events caused by pathogenic host responses. To treat these complications, their underlying etiology must be identified. Thus, a novel AI-based methodology, MOATAI-VIR, which predicts disease-protein-pathway relationships for 22 clinical manifestations attributed to COVID-19 was developed. SARS-CoV-2 interacting human proteins and GWAS identified respiratory failure associated risk genes provide the input from which the mode-of-action (MOA) proteins/pathways of the resulting disease comorbidities are predicted. These comorbidities are then mapped to their clinical manifestations. Three uncharacterized manifestation categories are found: neoplasms, mental and behavioral disorders, and congenital malformations, deformations, and chromosomal abnormalities. The prevalence of neoplasms suggests a possible association between COVID-19 and cancer, whether by shared molecular mechanisms between oncogenesis and viral replication, or perhaps, SARS-CoV-2 is an oncovirus. To assess the molecular basis of each manifestation, the proteins shared across each group of comorbidities were prioritized and subject to global pathway analysis. From these most frequent pathways, the molecular features associated with hallmark COVID-19 phenotypes, such as loss of sense of smell/taste, unusual neurological symptoms, cytokine storm, and blood clots were explored. Results of MOATAI-VIR are available for academic users at: http://pwp.gatech.edu/cssb/MOATAI-VIR/.

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Prediction of severe adverse events, modes of action and drug treatments for COVID-19’s complications

Scientific Reports ◽

10.1038/s41598-021-00368-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Courtney Astore ◽

Hongyi Zhou ◽

Joshy Jacob ◽

Jeffrey Skolnick

Keyword(s):

Adverse Events ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Molecular Features ◽

Disease Protein ◽

Human Proteins ◽

Drug Treatments ◽

Severe Adverse Events ◽

Approved Drugs ◽

Fda Approved Drugs

AbstractFollowing SARS-CoV-2 infection, some COVID-19 patients experience severe host driven adverse events. To treat these complications, their underlying etiology and drug treatments must be identified. Thus, a novel AI methodology MOATAI-VIR, which predicts disease-protein-pathway relationships and repurposed FDA-approved drugs to treat COVID-19’s clinical manifestations was developed. SARS-CoV-2 interacting human proteins and GWAS identified respiratory failure genes provide the input from which the mode-of-action (MOA) proteins/pathways of the resulting disease comorbidities are predicted. These comorbidities are then mapped to their clinical manifestations. To assess each manifestation’s molecular basis, their prioritized shared proteins were subject to global pathway analysis. Next, the molecular features associated with hallmark COVID-19 phenotypes, e.g. unusual neurological symptoms, cytokine storms, and blood clots were explored. In practice, 24/26 of the major clinical manifestations are successfully predicted. Three major uncharacterized manifestation categories including neoplasms are also found. The prevalence of neoplasms suggests that SARS-CoV-2 might be an oncovirus due to shared molecular mechanisms between oncogenesis and viral replication. Then, repurposed FDA-approved drugs that might treat COVID-19’s clinical manifestations are predicted by virtual ligand screening of the most frequent comorbid protein targets. These drugs might help treat both COVID-19’s severe adverse events and lesser ones such as loss of taste/smell.

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Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer

Cancers ◽

10.3390/cancers13164029 ◽

2021 ◽

Vol 13 (16) ◽

pp. 4029

Author(s):

Sandra Muñoz-Galván ◽

Amancio Carnero

Keyword(s):

Ovarian Cancer ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Therapy Resistance ◽

Omics Technologies ◽

Gynecological Malignancy ◽

Tumor Relapse ◽

Molecular Features ◽

Ovarian Cancers ◽

Late Detection

Ovarian cancer is a major cause of fatality due to a gynecological malignancy. This lethality is largely due to the unspecific clinical manifestations of ovarian cancer, which lead to late detection and to high resistance to conventional therapies based on platinum. In recent years, we have advanced our understanding of the mechanisms provoking tumor relapse, and the advent of so-called omics technologies has provided exceptional tools to evaluate molecular mechanisms leading to therapy resistance in ovarian cancer. Here, we review the contribution of genomics, transcriptomics, and epigenomics techniques to our knowledge about the biology and molecular features of ovarian cancers, with a focus on therapy resistance. The use of these technologies to identify molecular markers and mechanisms leading to chemoresistance in these tumors is discussed, as well as potential further applications.

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New Insights into Chikungunya Virus Infection and Pathogenesis

Annual Review of Virology ◽

10.1146/annurev-virology-091919-102021 ◽

2021 ◽

Vol 8 (1) ◽

Author(s):

Vasiliya Kril ◽

Olivier Aïqui-Reboul-Paviet ◽

Laurence Briant ◽

Ali Amara

Keyword(s):

Chikungunya Virus ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Annual Review ◽

Publication Date ◽

Nonstructural Proteins ◽

Chikv Infection ◽

Replication Complex ◽

Host Cell Interactions ◽

Patients Experience

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus responsible for major outbreaks of disease since 2004 in the Indian Ocean islands, South east Asia, and the Americas. CHIKV causes debilitating musculoskeletal disorders in humans that are characterized by fever, rash, polyarthralgia, and myalgia. The disease is often self-limiting and nonlethal; however, some patients experience atypical or severe clinical manifestations, as well as a chronic rheumatic syndrome. Unfortunately, no efficient antivirals against CHIKV infection are available so far, highlighting the importance of deepening our knowledge of CHIKV host cell interactions and viral replication strategies. In this review, we discuss recent breakthroughs in the molecular mechanisms that regulate CHIKV infection and lay down the foundations to understand viral pathogenesis. We describe the role of the recently identified host factors co-opted by the virus for infection and pathogenesis, and emphasize the importance of CHIKV nonstructural proteins in both replication complex assembly and host immune response evasion. Expected final online publication date for the Annual Review of Virology, Volume 8 is September 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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High-Throughput Phenotyping Toolkit for Characterizing Cellular Models of Hypertrophic Cardiomyopathy in Vitro

Methods and Protocols ◽

10.3390/mps2040083 ◽

2019 ◽

Vol 2 (4) ◽

pp. 83 ◽

Cited By ~ 4

Author(s):

Mosqueira ◽

Lis-Slimak ◽

Denning

Keyword(s):

Hypertrophic Cardiomyopathy ◽

High Throughput ◽

Molecular Mechanisms ◽

Clinical Manifestations ◽

Cellular Models ◽

Molecular Features ◽

High Throughput Drug Screening ◽

High Throughput Phenotyping ◽

Screening Approaches

Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular disease characterised by multifarious hallmarks, a heterogeneous set of clinical manifestations, and several molecular mechanisms. Various disease models have been developed to study this condition, but they often show contradictory results, due to technical constraints and/or model limitations. Therefore, new tools are needed to better investigate pathological features in an unbiased and technically refined approach, towards improving understanding of disease progression. Herein, we describe three simple protocols to phenotype cellular models of HCM in vitro, in a high-throughput manner where technical artefacts are minimized. These are aimed at investigating: (1) Hypertrophy, by measuring cell volume by flow cytometry; (2) HCM molecular features, through the analysis of a hypertrophic marker, multinucleation, and sarcomeric disarray by high-content imaging; and (3) mitochondrial respiration and content via the Seahorse™ platform. Collectively, these protocols comprise straightforward tools to evaluate molecular and functional parameters of HCM phenotypes in cardiomyocytes in vitro. These facilitate greater understanding of HCM and high-throughput drug screening approaches and are accessible to all researchers of cardiac disease modelling. Whilst HCM is used as an exemplar, the approaches described are applicable to other cellular models where the investigation of identical biological changes is paramount.

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Real world experience in 150 genotype 1 HCV patients with triple therapy: severe adverse events and high rates of virological failure in cirrhotic patients with portal hypertension (platelets < 100.000/nl and albumine < 40 g/l)

Zeitschrift für Gastroenterologie ◽

10.1055/s-0033-1352750 ◽

2013 ◽

Vol 51 (08) ◽

Author(s):

J Petersen ◽

K Voelker ◽

K Olah ◽

K Matschenz ◽

H Wolski ◽

...

Keyword(s):

Portal Hypertension ◽

Adverse Events ◽

Triple Therapy ◽

Virological Failure ◽

Real World ◽

Genotype 1 ◽

Cirrhotic Patients ◽

Severe Adverse Events

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PRE-THERAPEUTIC NUTRITIONAL STATUS FOLLOW-UP FOR PREDICTING SEVERE ADVERSE EVENTS IN PATIENTS WITH CERVICAL CANCER TREATED BY CHEMO-RADIOTHERAPY

10.26226/morressier.599bdc7bd462b80296ca0b4c ◽

2017 ◽

Author(s):

Ester Miralpeix

Keyword(s):

Cervical Cancer ◽

Adverse Events ◽

Nutritional Status ◽

Severe Adverse Events

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Faculty Opinions recommendation of Severe adverse events after cataract surgery among medicare beneficiaries.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13293964.14655054 ◽

2011 ◽

Author(s):

Mark Packer ◽

Sanja Dragovic

Keyword(s):

Adverse Events ◽

Cataract Surgery ◽

Medicare Beneficiaries ◽

Severe Adverse Events

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Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

Journal of Clinical Medicine ◽

10.3390/jcm10061214 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1214

Author(s):

Ji Tu ◽

Jose Vargas Castillo ◽

Abhirup Das ◽

Ashish D. Diwan

Keyword(s):

Cervical Myelopathy ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Imaging Techniques ◽

Disease Process ◽

Classification Systems ◽

Molecular Features ◽

Formidable Challenge ◽

Long Term Treatment ◽

Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

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Vitamin D Deficiency in Testicular Cancer Survivors: A Systematic Review

International Journal of Molecular Sciences ◽

10.3390/ijms22105145 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5145

Author(s):

Giuseppe Schepisi ◽

Caterina Gianni ◽

Sara Bleve ◽

Silvia De Padova ◽

Cecilia Menna ◽

...

Keyword(s):

Vitamin D ◽

Testicular Cancer ◽

Vitamin D Deficiency ◽

Molecular Mechanisms ◽

Hypovitaminosis D ◽

Young Males ◽

Report Data ◽

Testicular Cancer Survivors ◽

Patients Experience

Testicular cancer (TC) is the most frequent tumor in young males. In the vast majority of cases, it is a curable disease; therefore, very often patients experience a long survival, also due to their young age at diagnosis. In the last decades, the role of the vitamin D deficiency related to orchiectomy has become an increasingly debated topic. Indeed, vitamin D is essential in bone metabolism and many other metabolic pathways, so its deficiency could lead to various metabolic disorders especially in long-term TC survivors. In our article, we report data from studies that evaluated the incidence of hypovitaminosis D in TC survivors compared with cohorts of healthy peers and we discuss molecular mechanisms and clinical implications.

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