scholarly journals ATP6V1B2 and IFI27 and their intrinsic functional genomic characteristics associated with SARS-CoV-2

2022 ◽  
Author(s):  
Zhengjun Zhang
Keyword(s):  
Medical Research ◽  
Transcriptional Response ◽  
Disease Status ◽  
Antiviral Drugs ◽  
Functional Genomic ◽  
Blood Samples ◽  
Essential Step ◽  
Number Of Genes

Genes functionally associated with SARS-CoV-2 and genes functionally related to COVID-19 disease can be different, whose distinction will become the first essential step for successfully fighting against the COVID-19 pandemic. Unfortunately, this first step has not been completed in all biological and medical research. Using a newly developed max-competing logistic classifier, two genes, ATP6V1B2 and IFI27, stand out to be critical in transcriptional response to SARS-CoV-2 with differential expressions derived from NP/OP swab PCR. This finding is evidenced by combining these two genes with one another gene in predicting disease status to achieve better-indicating power than existing classifiers with the same number of genes. In addition, combining these two genes with three other genes to form a five-gene classifier outperforms existing classifiers with ten or more genes. With their exceptional predicting power, these two genes can be critical in fighting against the COVID-19 pandemic as a new focus and direction. Comparing the functional effects of these genes with a five-gene classifier with 100% accuracy identified and tested from blood samples in the literature, genes and their transcriptional response and functional effects to SARS-CoV-2 and genes and their functional signature patterns to COVID-19 antibody are significantly different, which can be interpreted as the former is the point of a phenomenon, and the latter is the essence of the disease. Such significant findings can help explore the causal and pathological clue between SARS-CoV-2 and COVID-19 disease and fight against the disease with more targeted vaccines, antiviral drugs, and therapies.

scholarly journals Transcriptomic signals in blood prior to lung cancer focusing on time to diagnosis and metastasis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Therese H. Nøst ◽  
Marit Holden ◽  
Tom Dønnem ◽  
Hege Bøvelstad ◽  
Charlotta Rylander ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Diagnosis ◽  
Metastatic Cancer ◽  
Case Control ◽  
Functional Genomic ◽  
Blood Samples ◽  
Lung Cancer Diagnosis ◽  
Time To Diagnosis ◽  
Genomic Signals ◽  
Nested Case Control

AbstractRecent studies have indicated that there are functional genomic signals that can be detected in blood years before cancer diagnosis. This study aimed to assess gene expression in prospective blood samples from the Norwegian Women and Cancer cohort focusing on time to lung cancer diagnosis and metastatic cancer using a nested case–control design. We employed several approaches to statistically analyze the data and the methods indicated that the case–control differences were subtle but most distinguishable in metastatic case–control pairs in the period 0–3 years prior to diagnosis. The genes of interest along with estimated blood cell populations could indicate disruption of immunological processes in blood. The genes identified from approaches focusing on alterations with time to diagnosis were distinct from those focusing on the case–control differences. Our results support that explorative analyses of prospective blood samples could indicate circulating signals of disease-related processes.

scholarly journals Molecular Alterations in Basal Cell Carcinoma Subtypes

2021 ◽  
Author(s):  
Lucia Di Nardo ◽  
Cristina Pellegrini ◽  
Alessandro Di Stefani ◽  
Francesco Ricci ◽  
Barbara Fossati ◽  
...  
Keyword(s):  
Basal Cell Carcinoma ◽  
Sun Exposure ◽  
Therapeutic Strategies ◽  
Blood Samples ◽  
Molecular Alterations ◽  
Depth Analysis ◽  
Number Of Genes ◽  
Superficial Type ◽  
Tumorigenic Mechanism ◽  
Head Neck

Abstract A number of genes have been implicated in the pathogenesis of BCC in addition to the Hedgehog pathway, which is known to drive the initiation of this tumour.We performed in-depth analysis of 13 BCC-related genes (CSMD1, CSMD2, DPH3 promoter, PTCH1, SMO, GLI1, NOTCH1, NOTCH2, TP53, ITIH2, DPP10, STEAP4, TERT promoter) in 57 BCC lesions (26 superficial and 31 nodular) from 55 patients and their corresponding blood samples. PTCH1 and TP53 mutations were found in 71.9% and 45.6% of BCCs, respectively. A high mutation rate was also detected in CSMD1 (63.2%), NOTCH1 (43.8%) and DPP10 (35.1%), and frequent non-coding mutations were identified in TERT (57.9%) and DPH3 promoter (49.1%). CSMD1 mutations significantly co-occurred with TP53 changes (p=0.002). A significant association was observed between the superficial type of BCC and PTCH1 (p=0.017) and NOTCH1 (p=0.018) mutations. In addition, PTCH1 mutations were significantly associated with intermittent sun exposure (p=0.046) and the occurrence of single lesions (p=0.021), while NOTCH1 mutations were more frequent in BCCs located on the trunk compared to the head/neck and extremities (p=0.001).In conclusion, we provide further insights into the molecular alterations underlying the tumorigenic mechanism of superficial and nodular BCCs with a view towards novel rationale-based therapeutic strategies.

scholarly journals CITED1 is a novel binding partner of MITF that influences the MITF-directed transcriptional profile in melanoma

2017 ◽  
Author(s):  
Barbara Lettiero ◽  
Martin Lauss ◽  
Ake Borg ◽  
Sofia Gruvberger-Saal ◽  
Goran B Jönsson ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Gene Signature ◽  
Melanoma Cells ◽  
Cell Phenotype ◽  
Chromatin Binding ◽  
Binding Partner ◽  
Nuclear Complex ◽  
Number Of Genes ◽  
First Time

We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.

Immune checkpoint molecule expression measured using circulating cell-free RNA isolated from the blood of metastatic prostate cancer patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 380-380
Author(s):  
Kanthi Athreya Kollengode ◽  
Erwin Grussie ◽  
Genevieve Danenberg ◽  
Joshua L. Usher ◽  
KATHLEEN DANENBERG ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Negative Correlation ◽  
Immune Checkpoint ◽  
Metastatic Prostate Cancer ◽  
Disease Status ◽  
Significant Negative Correlation ◽  
Gene Expressions ◽  
Blood Samples ◽  
Group A

380 Background: Recent studies have identified panels of immune-related genes linked to progression and survival. Expressions usually are measured using RNA from tissue samples. The aim of the present study was to utilize circulating RNA (cfRNA) isolated from hormone-naïve (HN) and castrate-resistant prostate cancer (CRPC) patients to measure gene expressions of PD-L1, cytotoxic T-lymphocyte associated protein 4 (CTLA-4), T-cell immunoglobulin and mucin domain 3 (TIM-3) and lymphocyte activated gene 3 (LAG-3). Androgen receptor (AR) and AR-variant 7 (AR-v7) expressions were also measured in these samples to test for any possible relationships with the immune checkpoint genes. Methods: Blood samples were collected from 53 metastatic prostate cancer patients. cfRNA was extracted from patients’ plasma and reverse transcribed into complementary DNA. The gene expressions (mRNA levels) of the above genes were determined by quantitative reverse transcription-PCR. Beta-actin was used to normalize gene expressions to total RNA content. Results: Each of the immune signatures tested (PD-L1, TIM-3, LAG-3, CTLA-4) was expressed in over 50% (29/53) of the patients’ blood samples. AR was expressed in 25/53 (47%) samples. Four of these patients (8%) expressed AR-v7, indicating resistance to anti-AR drugs. Patient disease status included: 25% (13/53) CRPC, 74% (39/53) HN, and 1 unknown. Within the CRPC group, a significant negative correlation was found between TIM-3 and CTLA-4 expression (-0.833), and CTLA-4 also correlated with disease progression (0.719). Within the HN group, a significant negative correlation was measured between TIM-3 and PD-L1 (0.589). AR expression did not correlate with other targets measured among all patients or within the CRPC or HN groups. Conclusions: This study demonstrates successful quantitation of immune checkpoint gene expressions as well the AR and AR-v7 genes in plasma of prostate cancer patients. This result opens the possibility of the use of a noninvasive method to measure, monitor and track the dynamic interplay of these genes with changing disease status. Clinical trial information: NCT02853097.

scholarly journals A Positive Regulatory Loop Controls Expression of the Locus of Enterocyte Effacement-Encoded Regulators Ler and GrlA

2005 ◽  
Vol 187 (23) ◽  
pp. 7918-7930 ◽  
Author(s):  
Jeannette Barba ◽  
Víctor H. Bustamante ◽  
Mario A. Flores-Valdez ◽  
Wanyin Deng ◽  
B. Brett Finlay ◽  
...  
Keyword(s):  
Pathogenic Bacteria ◽  
Virulence Genes ◽  
Intestinal Epithelial Cells ◽  
Transcriptional Response ◽  
Transcriptional Regulators ◽  
Intestinal Epithelial ◽  
Regulatory Motifs ◽  
Essential Step ◽  
Enterocyte Effacement ◽  
Regulatory Loop

ABSTRACT The formation of attaching and effacing (A/E) lesions on intestinal epithelial cells is an essential step in the pathogenesis of human enteropathogenic and enterohemorrhagic Escherichia coli and of the mouse pathogen Citrobacter rodentium. The genes required for the development of the A/E phenotype are located within a pathogenicity island known as the locus of enterocyte effacement (LEE). The LEE-encoded transcriptional regulators Ler, an H-NS-like protein, and GrlA, a member of a novel family of transcriptional activators, positively control the expression of the genes located in the LEE and their corresponding virulence. In this study, we used C. rodentium as a model to study the mechanisms controlling the expression of Ler and GrlA. By deletion analysis of the ler and grlRA regulatory regions and complementation experiments, negative and positive cis-acting regulatory motifs were identified that are essential for the regulation of both genes. This analysis confirmed that GrlA is required for the activation of ler, but it also showed that Ler is required for the expression of grlRA, revealing a novel regulatory loop controlling the optimal expression of virulence genes in A/E pathogens. Furthermore, our results indicate that Ler and GrlA induce the expression of each other by, at least in part, counteracting the repression mediated by H-NS. However, whereas GrlA is still required for the optimal expression of ler even in the absence of H-NS, Ler is not needed for the expression of grlRA in the absence of H-NS. This type of transcriptional positive regulatory loop represents a novel mechanism in pathogenic bacteria that is likely required to maintain an appropriate spatiotemporal transcriptional response during infection.

scholarly journals Sequential Circulating Tumor Cell Counts in Patients with Locally Advanced or Metastatic Hepatocellular Carcinoma: Monitoring the Treatment Response

2020 ◽  
Vol 9 (1) ◽  
pp. 188 ◽  
Author(s):  
Kun-Ming Rau ◽  
Chien-Ting Liu ◽  
Yu-Chiao Hsiao ◽  
Kai-Yin Hsiao ◽  
Tzu-Min Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Treatment Response ◽  
Locally Advanced ◽  
Elevated Serum ◽  
Disease Status ◽  
Circulating Tumor Cell ◽  
Interquartile Range ◽  
Patient Treatment ◽  
Blood Samples ◽  
Cell Counts

Hepatocellular carcinoma (HCC) is among the most common causes of cancer death in men. Whether or not a longitudinal follow-up of circulating tumor cells (CTCs) before and at different time points during systemic/targeted therapy is useful for monitoring the treatment response of patients with locally advanced or metastatic HCC has been evaluated in this study. Blood samples (n = 104) were obtained from patients with locally advanced or metastatic HCC (n = 30) for the enrichment of CTCs by a negative selection method. Analysis of the blood samples from patients with defined disease status (n = 81) revealed that those with progressive disease (PD, n = 37) had significantly higher CTC counts compared to those with a partial response (PR) or stable disease (SD; n = 44 for PR + SD, p = 0.0002). The median CTC count for patients with PD and for patients with PR and SD was 50 (interquartile range 21–139) and 15 (interquartile range 4–41) cells/mL of blood, respectively. A longitudinal analysis of patients (n = 17) after a series of blood collections demonstrated that a change in the CTC count correlated with the patient treatment response in most of the cases and was particularly useful for monitoring patients without elevated serum alpha-fetoprotein (AFP) levels. Sequential CTC enumeration during treatment can supplement standard medical tests and benefit the management of patients with locally advanced or metastatic HCC, in particular for the AFP-low cases.

scholarly journals CITED1 is a novel binding partner of MITF that influences the MITF-directed transcriptional profile in melanoma

2017 ◽  
Author(s):  
Barbara Lettiero ◽  
Martin Lauss ◽  
Ake Borg ◽  
Sofia Gruvberger-Saal ◽  
Goran B Jönsson ◽  
...  
Keyword(s):  
Transcriptional Response ◽  
Gene Signature ◽  
Melanoma Cells ◽  
Cell Phenotype ◽  
Chromatin Binding ◽  
Binding Partner ◽  
Nuclear Complex ◽  
Number Of Genes ◽  
First Time

We previously demonstrated how CITED1 knockdown in melanoma cells had the capacity to perturb expression of a significant number of genes that comprised MITF and several of its known transcriptional targets. This manifest as a switch from a more invasive to a more proliferative gene signature phenotype. We now demonstrate by using MITF ChIP-seq, that altered CITED1 expression affects MITF transcription factor binding to its targets across the genome. We show that silencing CITED1 effectively amplifies the MITF chromatin-binding signal response while we also demonstrate for the first time that CITED1 and MITF co-localise in a nuclear complex using an in-situ ligation proximity assay. We propose that CITED1-MITF binding is capable of altering both the affinity of chromatin association and transcriptional response to MITF at the target regions in the genome where MITF is either directly or indirectly bound to DNA. As CITED1/SMAD2 has been shown to mediate TGFβ-driven transcription that induces amoeboid-like invasion in melanoma cells we hypothesis that the MITF/CITED1 driven transcriptional response dominates in MITF-high/low-invasive environment or proliferative signature cell phenotype, whereas the SMAD2/CITED1 transcriptional response is dominant in a low-MITF/ high-invasive signature environment.

scholarly journals Adaption and Degradation Strategies of Methylotrophic 1,4-Dioxane Degrading Strain Xanthobacter sp. YN2 Revealed by Transcriptome-Scale Analysis

2021 ◽  
Vol 22 (19) ◽  
pp. 10435
Author(s):  
Yingning Wang ◽  
Fang Ma ◽  
Jixian Yang ◽  
Haijuan Guo ◽  
Delin Su ◽  
...  
Keyword(s):  
Degradation Mechanism ◽  
Transcriptional Response ◽  
Malate Synthase ◽  
Expression Of Genes ◽  
Component Systems ◽  
Number Of Genes ◽  
Glyoxylate Metabolism ◽  
Genes Encoding ◽  
Two Component Systems ◽  
Underlying Mechanisms

Biodegradation of 1,4-dioxane (dioxane) contamination has gained much attention for decades. In our previous work, we isolated a highly efficient dioxane degrader, Xanthobacter sp. YN2, but the underlying mechanisms of its extraordinary degradation performance remained unresolved. In this study, we performed a comparative transcriptome analysis of YN2 grown on dioxane and citrate to elucidate its genetic degradation mechanism and investigated the transcriptomes of different dioxane degradation stages (T0, T24, T48). We also analyzed the transcriptional response of YN2 over time during which the carbon source switched from citrate to dioxane. The results indicate that strain YN2 was a methylotroph, which provides YN2 a major advantage as a pollutant degrader. A large number of genes involved in dioxane metabolism were constitutively expressed prior to dioxane exposure. Multiple genes related to the catabolism of each intermediate were upregulated by treatment in response to dioxane. Glyoxylate metabolism was essential during dioxane degradation by YN2, and the key intermediate glyoxylate was metabolized through three routes: glyoxylate carboligase pathway, malate synthase pathway, and anaplerotic ethylmalonyl–CoA pathway. Genes related to quorum sensing and transporters were significantly upregulated during the early stages of degradation (T0, T24) prior to dioxane depletion, while the expression of genes encoding two-component systems was significantly increased at late degradation stages (T48) when total organic carbon in the culture was exhausted. This study is the first to report the participation of genes encoding glyoxalase, as well as methylotrophic genes xoxF and mox, in dioxane metabolism. The present study reveals multiple genetic and transcriptional strategies used by YN2 to rapidly increase biomass during growth on dioxane, achieve high degradation efficiency and tolerance, and adapt to dioxane exposure quickly, which provides useful information regarding the molecular basis for efficient dioxane biodegradation.

The Prevalence of Vitamin D Deficiency in Impoverished Communities in Northern Lima, Peru

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Adam Samuel Kramer ◽  
Michaella Thomas ◽  
Andrew Makowski ◽  
David Drozek
Keyword(s):  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Skin Pigmentation ◽  
Geographic Location ◽  
Disease Status ◽  
Cross Sectional ◽  
Endocrine Society ◽  
Blood Samples ◽  
Vitamin D Levels ◽  
College Of Osteopathic Medicine

Context: Vitamin D deficiency is a global concern. There are many factors that affect the levels of vitamin D including demographics, gender, skin pigmentation, geographic location, and body mass index (BMI). In Lima, Peru, vitamin D levels may be influenced by ethnicity, socioeconomic status, overcrowded conditions, air pollution, and chronic disease status. Objective: The purpose of this cross-sectional study was to measure the prevalence of vitamin D deficiency and insufficiency in a sample of impoverished adults living in northern Lima. It was hypothesized that more than 40% of the study sample would have deficient levels of vitamin D. The Endocrine Society defines deficient levels asbeing < 20 ng/mL of 25(OH)D3, insufficient being 21–29 ng/mL of 25(OH)D3. Methods: In June 2016, a Global Health team from Ohio University Heritage College of Osteopathic Medicine provided medical clinics in impoverished communities in northern Lima. From a random sample of consenting adults, finger stick capillary blood samples were applied to Whatman protein saver cards and subsequently dried.Dried blood samples were punched, extracted, and analyzed by liquid chromatography tandem mass spectrometry. Participants had BMI measured as well. Results: 25(OH)D3 samples were obtained from 144 adults, 116 (80.6%) women, 20 (13.9%) men, 8 (5.6%) unspecified gender, age range of 18–94 with a mean of 39  years. In 66 patients (45.8%), 25(OH)D3 was deficient. In 74 patients (51.4%), 25(OH)D3 was insufficient. In 4 patients (2.8%), 25(OH)D3 was sufficient. For the women, 57 (49.1%) were deficient, 56 (48.3%) insufficient. For the men, 7 (35%) were deficient, 13 (65%) insufficient. Mean BMI was 27.3, with a range of 17.3–43.3; 40.3% were overweight and 23.6% were obese. No relationship between vitamin D levels and gender was identified (p = 0.203). There was no significant association betweenBMI levels and vitamin D levels (p = 0.418). Conclusions: In this sample, nearly one half of those tested had deficient levels of 25(OH)D3, with the vast majority (97%) having less than sufficient levels. This study population also demonstrated an average BMI of 27.3. Further study is needed to clarify the role of vitamin D as a therapeutic and its relationship with BMI.

scholarly journals Blood and tissue neuroendocrine tumor gene cluster analysis correlate, define hallmarks and predict disease status

2015 ◽  
Vol 22 (4) ◽  
pp. 561-575 ◽  
Author(s):  
Mark Kidd ◽  
Ignat Drozdov ◽  
Irvin Modlin
Keyword(s):  
Neuroendocrine Tumor ◽  
Activity Index ◽  
Principal Component ◽  
Disease Status ◽  
Gene Clusters ◽  
Linear Modeling ◽  
Blood Samples ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

A multianalyte algorithmic assay (MAAA) identifies circulating neuroendocrine tumor (NET) transcripts (n=51) with a sensitivity/specificity of 98%/97%. We evaluated whether blood measurements correlated with tumor tissue transcript analysis. The latter were segregated into gene clusters (GC) that defined clinical ‘hallmarks’ of neoplasia. A MAAA/cluster integrated algorithm (CIA) was developed as a predictive activity index to define tumor behavior and outcome. We evaluated three groups. Group 1: publically available NET transcriptome databases (n=15; GeneProfiler). Group 2: prospectively collected tumors and matched blood samples (n=22; qRT-PCR). Group 3: prospective clinical blood samples,n=159: stable disease (SD):n=111 and progressive disease (PD):n=48. Regulatory network analysis, linear modeling, principal component analysis (PCA), and receiver operating characteristic analyses were used to delineate neoplasia ‘hallmarks’ and assess GC predictive utility. Our results demonstrated: group 1: NET transcriptomes identified (92%) genes elevated. Group 2: 98% genes elevated by qPCR (fold change >2,P<0.05). Correlation analysis of matched blood/tumor was highly significant (R2=0.7,P<0.0001), and 58% of genes defined nine omic clusters (SSTRome, proliferome, signalome, metabolome, secretome, epigenome, plurome, and apoptome). Group 3: six clusters (SSTRome, proliferome, metabolome, secretome, epigenome, and plurome) differentiated SD from PD (area under the curve (AUC)=0.81). Integration with blood-algorithm amplified the AUC to 0.92±0.02 for differentiating PD and SD. The CIA defined a significantly lower SD score (34.1±2.6%) than in PD (84±2.8%,P<0.0001). In conclusion, circulating transcripts measurements reflect NET tissue values. Integration of biologically relevant GC differentiate SD from PD. Combination of GC data with the blood-algorithm predicted disease status in >92%. Blood transcript measurement predicts NET activity.

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