Search

Public gene expression databases are a rapidly expanding resource of organism responses to diverse perturbations, presenting both an opportunity and a challenge for bioinformatics workflows to extract actionable knowledge of transcription regulatory network function. Here, we introduce a five-step computational pipeline, called iModulonMiner, to compile, process, curate, analyze, and characterize the totality of RNA-seq data for a given organism or cell type. This workflow is centered around the data-driven computation of co-regulated gene sets using Independent Component Analysis, called iModulons, which have been shown to have broad applications. As a demonstration, we applied this workflow to generate the iModulon structure of Bacillus subtilis using all high-quality, publicly-available RNA-seq data. Using this structure, we predicted regulatory interactions for multiple transcription factors, identified groups of co-expressed genes that are putatively regulated by undiscovered transcription factors, and predicted properties of a recently discovered single-subunit phage RNA polymerase. We also present a Python package, PyModulon, with functions to characterize, visualize, and explore computed iModulons. The pipeline, available at https://github.com/SBRG/iModulonMiner, can be readily applied to diverse organisms to gain a rapid understanding of their transcriptional regulatory network structure and condition-specific activity., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Sastry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Little is known about factors associated with the severity of cleft lip with or without cleft palate (CL/P) especially during the COVID-19 pandemic with its dramatic changes., Objectives: The aim of this multi-national study is to measure the association between CL/P severity, COVID-19 infection, and fear of COVID-19 in five Arab countries., Methods: This cross-sectional study took place in major governmental hospitals in five Arab countries from November 2020 to April 2023. Participants were infants born with CL/P and their mothers who were in their 1st trimester during the COVID-19 pandemic. Clinical examination was carried out, and CL/P cases were grouped according to phenotype: cleft lip and palate (CLP) versus cleft lip (CL), cleft extension (incomplete versus complete), and site (unilateral versus bilateral) to assess severity. Information on maternal COVID-19 infection and fear of COVID-19 were gathered., Results: The study recruited 273 CL/P infants. Maternal COVID-19 infection during one-month pre-gestation and 1st trimester was significantly associated with higher odds of CL/P severity (AOR = 2.707; P = 0.002) than mothers without the COVID-19 infection. Using supplements during pregnancy showed a protective effect (AOR = 0.573; P = 0.065)., Conclusion: Mothers infected with COVID-19 before and during pregnancy had more than twofold higher odds of having an infant with a more severe CL/P phenotype., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Synechococcus elongatus is an important cyanobacterium that serves as a versatile and robust model for studying circadian biology and photosynthetic metabolism. Its transcriptional regulatory network (TRN) is of fundamental interest, as it orchestrates the cell's adaptation to the environment, including its response to sunlight. Despite the previous characterization of constituent parts of the S. elongatus TRN, a comprehensive layout of its topology remains to be established. Here, we decomposed a compendium of 300 high-quality RNA sequencing datasets of the model strain PCC 7942 using independent component analysis. We obtained 57 independently modulated gene sets, or iModulons, that explain 67% of the variance in the transcriptional response and 1) accurately reflect the activity of known transcriptional regulations, 2) capture functional components of photosynthesis, 3) provide hypotheses for regulon structures and functional annotations of poorly characterized genes, and 4) describe the transcriptional shifts under dynamic light conditions. This transcriptome-wide analysis of S. elongatus provides a quantitative reconstruction of the TRN and presents a knowledge base that can guide future investigations. Our systems-level analysis also provides a global TRN structure for S. elongatus PCC 7942., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aim: Chronic wounds, defined as wounds that do not heal in a logical set of stages, impact patients' quality of life by disrupting their self-esteem, sleep, social interaction, work capacity, and psychological well-being. Chronic wounds are a prevalent problem in Oman due to the high number of patients with diabetes, sickle cell disease, road traffic accidents, and decubitus ulcer. Therefore, it is paramount to analyse the health-related quality of life (HRQOL) of these patients with chronic wounds., Material and Methods: An observational, cross-sectional, descriptive study with a quantitative approach was conducted among 275 adult patients with chronic wounds in three tertiary hospitals of Muscat from June to December 2021 using a self-reported Cardiff life wound impact questionnaire and the Bates-Jensen wound assessment tool. Data were analysed with IBM SPSS version 23 using inferential statistics and chi-square test., Results: We found that the majority of participants were men (178; 64.7 %), aged between 41 and 60 years (107; 38.9 %), predominantly with diabetic wounds (80; 29.1 %). Respondents reported poor HRQOL across all domains: well-being (63.24 ± 18.092), physical (53.24 ± 18.387), and social (59.54 ± 19.025). Statistically significant poorer HRQOL was observed among the elderly above 60 years, illiterates, those with traumatic wounds, and those receiving medication and dressing as treatment., Conclusions: Our findings indicate that Omani patients with chronic wounds experience low HRQOL. It is imperative for healthcare providers to offer comprehensive care to these patients. To enhance their quality of life and alleviate suffering, evaluating both the wounds and HRQOL is essential. Such assessments will enable the optimisation of treatment and coping strategies for patients., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Tissue Viability Society / Society of Tissue Viability. Published by Elsevier Ltd. All rights reserved.)

Objectives: Risk factors for non-syndromic orofacial cleft (NSOFCs) include genetic profile and environmental exposure to medication and illnesses during pregnancy. We assessed the association between the COVID-19 vaccination and the incidence of NSOFC across five Middle Eastern countries., Materials and Methods: This multi-country, hospital-based, case-control study included infants with NSOFCs whose first 3 intrauterine months coincided with the time when pregnant women were allowed to receive COVID-19 vaccination in the countries participating in the study. Newborns with NSOFCs were examined for cleft type and their parents were interviewed for maternal exposures and COVID-19 vaccination. Controls were newborns matched to cases in gender and setting., Results: The study recruited 977 (348 children with NSOFCs and 629 controls). Maternal use of nicotine (Adjusted Odds Ratio (AOR): 2.437; P = 0.044) and family history of NSOFC (AOR: 11.059; P < 0.001) increased significantly the AOR of having a child with NSOFC. On the other hand, COVID-19 vaccine administration to pregnant mothers have significantly decreased the AOR of having a child with NSOFC (AOR: 0.337; P = 0.006)., Conclusion: This study suggests that COVID-19 vaccination is not related to NSOFC and might protect against having a child affected with such a congenital anomaly., Clinical Relevance: The finding of this study is important for healthcare providers for considering COVID-19 vaccination for pregnant woman. Clear communication and education about the potential risks and benefits would be crucial for informed decision-making. The study's results would directly impact pregnant individuals, as they would need accurate information to make informed decisions about their health and the health of their infants., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The environmental etiology of non-syndromic orofacial clefts (NSOFCs) is still under research. The aim of this case-control study is to assess COVID-19 associated factors that may be related to the risk of NSOFC in five Arab countries. These factors include COVID-19 infection, COVID-19 symptoms, family member or friends infected with COVID-19, stress, smoking, socioeconomic status and fear of COVID-19., Methods: The study took place in governmental hospitals in five Arab countries from November 2020 to November 2021. Controls are matched in the month of delivery and site of recruitment. A clinical examination was carried out using LASHAL classification. Maternal exposure to medication, illnesses, supplementation, COVID-19 infection during their pregestation and 1st trimester periods were evaluated using a validated questionnaire. Maternal exposure to stress was assessed using the Life Events scale, fear of covid-19 scale, family member or friend affected with covid-19 infection, pregnancy planning and threatened abortion., Results: The study recruited 1135 infants (386 NSOFC and 749 controls). Living in urban areas, maternal exposure to medications 3-months pregestation, maternal exposure to any of the prenatal life events and maternal fear of COVID-19 significantly increased the risk of having a child with NSOFC. On the other hand, mothers exposed to supplementation 3-months pregestation, mothers suspected of having COVID-19 infection, family members or friends testing positive with COVID-19 significantly decreased the risk of having a child with NSOFC., Conclusions: This study suggests that NSOFC may be associated with maternal exposure to lifetime stress and COVID-19 fear in particular, with no direct effect of the COVID-19 infection itself. This highlights the importance of providing psychological support for expecting mothers during stressful events that affect populations such as the COVID-19 pandemic, in addition to the usual antenatal care., (© 2023. The Author(s).)

Establishing transcriptional regulatory networks (TRNs) in bacteria has been limited to well-characterized model strains. Using machine learning methods, we established the transcriptional regulatory networks of six Salmonella enterica serovar Typhimurium strains from their transcriptomes. By decomposing a compendia of RNA sequencing (RNA-seq) data with independent component analysis, we obtained 400 independently modulated sets of genes, called iModulons. We (i) performed pan-genome analysis of the phylogroup structure of S . Typhimurium and analyzed the iModulons against this background, (ii) revealed different genetic signatures in pathogenicity islands that explained phenotypes, (iii) discovered three transport iModulons linked to antibiotic resistance, (iv) described concerted responses to cationic antimicrobial peptides, and (v) uncovered new regulons. Thus, by combining pan-genome and transcriptomic analytics, we revealed variations in TRNs across six strains of serovar Typhimurium. IMPORTANCE Salmonella enterica serovar Typhimurium is a pathogen involved in human nontyphoidal infections. Treating S . Typhimurium infections is difficult due to the species's dynamic adaptation to its environment, which is dictated by a complex transcriptional regulatory network (TRN) that is different across strains. In this study, we describe the use of independent component analysis to characterize the differential TRNs across the S . Typhimurium pan-genome using a compendium of high-quality RNA-seq data. This approach provided unprecedented insights into the differences between regulation of key cellular functions and pathogenicity in the different strains. The study provides an impetus to initiate a large-scale effort to reveal the TRN differences between the major phylogroups of the pathogenic bacteria, which could fundamentally impact personalizing treatments of bacterial pathogens.

Mycobacterium tuberculosis is one of the most consequential human bacterial pathogens, posing a serious challenge to 21st century medicine. A key feature of its pathogenicity is its ability to adapt its transcriptional response to environmental stresses through its transcriptional regulatory network (TRN). While many studies have sought to characterize specific portions of the M. tuberculosis TRN, and some studies have performed system-level analysis, few have been able to provide a network-based model of the TRN that also provides the relative shifts in transcriptional regulator activity triggered by changing environments. Here, we compiled a compendium of nearly 650 publicly available, high quality M. tuberculosis RNA-sequencing data sets and applied an unsupervised machine learning method to obtain a quantitative, top-down TRN. It consists of 80 independently modulated gene sets known as "iModulons," 41 of which correspond to known regulons. These iModulons explain 61% of the variance in the organism's transcriptional response. We show that iModulons (i) reveal the function of poorly characterized regulons, (ii) describe the transcriptional shifts that occur during environmental changes such as shifting carbon sources, oxidative stress, and infection events, and (iii) identify intrinsic clusters of regulons that link several important metabolic systems, including lipid, cholesterol, and sulfur metabolism. This transcriptome-wide analysis of the M. tuberculosis TRN informs future research on effective ways to study and manipulate its transcriptional regulation and presents a knowledge-enhanced database of all published high-quality RNA-seq data for this organism to date. IMPORTANCE Mycobacterium tuberculosis H37Rv is one of the world's most impactful pathogens, and a large part of the success of the organism relies on the differential expression of its genes to adapt to its environment. The expression of the organism's genes is driven primarily by its transcriptional regulatory network, and most research on the TRN focuses on identifying and quantifying clusters of coregulated genes known as regulons. While previous studies have relied on molecular measurements, in the manuscript we utilized an alternative technique that performs machine learning to a large data set of transcriptomic data. This approach is less reliant on hypotheses about the role of specific regulatory systems and allows for the discovery of new biological findings for already collected data. A better understanding of the structure of the M. tuberculosis TRN will have important implications in the design of improved therapeutic approaches.

The transcriptional regulatory network in prokaryotes controls global gene expression mostly through transcription factors (TFs), which are DNA-binding proteins. Chromatin immunoprecipitation (ChIP) with DNA sequencing methods can identify TF binding sites across the genome, providing a bottom-up, mechanistic understanding of how gene expression is regulated. ChIP provides indispensable evidence toward the goal of acquiring a comprehensive understanding of cellular adaptation and regulation, including condition-specificity. ChIP-derived data's importance and labor-intensiveness motivate its broad dissemination and reuse, which is currently an unmet need in the prokaryotic domain. To fill this gap, we present proChIPdb (prochipdb.org), an information-rich, interactive web database. This website collects public ChIP-seq/-exo data across several prokaryotes and presents them in dashboards that include curated binding sites, nucleotide-resolution genome viewers, and summary plots such as motif enrichment sequence logos. Users can search for TFs of interest or their target genes, download all data, dashboards, and visuals, and follow external links to understand regulons through biological databases and the literature. This initial release of proChIPdb covers diverse organisms, including most major TFs of Escherichia coli, and can be expanded to support regulon discovery across the prokaryotic domain., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Dynamic cellular responses to environmental constraints are coordinated by the transcriptional regulatory network (TRN), which modulates gene expression. This network controls most fundamental cellular responses, including metabolism, motility, and stress responses. Here, we apply independent component analysis, an unsupervised machine learning approach, to 95 high-quality Sulfolobus acidocaldarius RNA-seq datasets and extract 45 independently modulated gene sets, or iModulons. Together, these iModulons contain 755 genes (32% of the genes identified on the genome) and explain over 70% of the variance in the expression compendium. We show that five modules represent the effects of known transcriptional regulators, and hypothesize that most of the remaining modules represent the effects of uncharacterized regulators. Further analysis of these gene sets results in: (1) the prediction of a DNA export system composed of five uncharacterized genes, (2) expansion of the LysM regulon, and (3) evidence for an as-yet-undiscovered global regulon. Our approach allows for a mechanistic, systems-level elucidation of an extremophile's responses to biological perturbations, which could inform research on gene-regulator interactions and facilitate regulator discovery in S. acidocaldarius. We also provide the first global TRN for S. acidocaldarius . Collectively, these results provide a roadmap toward regulatory network discovery in archaea., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chauhan, Poudel, Rychel, Lamoureux, Yoo, Al Bulushi, Yuan, Palsson and Sastry.)

Teratomas can occur in almost any region of the body and are the most common extragonadal germ cell childhood tumors. However, craniofacial teratomas are rare. Craniofacial teratomas can present unique features and cause significant functional and aesthetic concerns. There are complex lesions that can have components intra-cranially and extra-cranially. Therefore, their management requires significant multi-stage multidisciplinary surgical procedures. Herein, we present a case of craniofacial teratoma in a child with the phenotype of proboscis lateralis that highlights some of the pertinent point of the diagnosis and management of congenital neonatal teratomas.

Background: The human hand is an important functional and sensory organ. Its complex anatomy reflects its important functional capabilities. Many Muslim countries observe the holy festivals with a traditional sacrifice of an animal in order to share the meat (basic commodity) with beloved ones. During such festivals hand injuries have been reported to increase. This study aimed to compare cases and controls of hand injuries treated at the national trauma center in the Sultanate of Oman during a 10-year time period., Methods: This is a case-control retrospective review for 10 years in the Sultanate of Oman. The cases were all hand injuries registered and assessed at Khoula Hospital in the Sultanate of Oman during the 3 days of both holy festivals from January 2004 to December 2013. Controls were hand injuries registered and assessed at Khoula Hospital in the Sultanate of Oman during nonfestival days. Data were extracted and collected from the Emergency Department database. A descriptive and comparative analysis was done., Results: There were 1091 cases reviewed in this study. Knife laceration was 2.4 more common during holy festivals than any other time. Extensor tendon injuries were 2.7 more common during holy festivals than nonfestival times. Thumb and index fingers constituted around 40% of the total injuries. Of all patients reviewed, 85% were treated and discharged home without admission., Conclusion: Holy festivals in the sultanate of Oman are risky times for hand injuries. Knife lacerations are more common during such times than any other times. Emergency and plastic services should be aware of the pattern of hand injuries during such times in order to prepare and plan services accordingly.

Cutaneous scarring is common after trauma, surgery and infection and occurs when normal skin tissue is replaced by fibroblastic tissue during the healing process. The pathophysiology of scar formation is not yet fully understood, although the degree of tension across the wound edges and the speed of cell growth are believed to play central roles. Prevention of scars is essential and can be achieved by attention to surgical techniques and the use of measures to reduce cell growth. Grading and classifying scars is important to determine available treatment strategies. This article presents an overview of the current therapies available for the prevention and treatment of scars. It is intended to be a practical guide for surgeons and other health professionals involved with and interested in scar management.

Aim: The aim of this study was to describe the epidemiology of burns admitted to the National Burns Unit (NBU) in the Sultanate of Oman between 1987 and 2011., Methods: This is a retrospective review of burn patients admitted to Oman's National Burns Unit (NBU) between 1987 and 2011. The data extracted from the national burn registry. The study describes the admission rate by gender and age groups, occupation, causes of burns, time-to-admission, length of stay and in-hospital mortality of burns between 1987 and 2011., Results: During a 25-year from 1987 to 2011, there were 3531 burn patients admitted to the National Burns Unit in Oman. The average admission rate to NBU is 7.02 per 100,000 persons per year. On average, males were more likely to be admitted to the NBU than females during the study period (P value < 0.04). Patients aged 1-10 years old constituted 46.6% of caseload during the study period. Flames and scalds caused 88.4% of burns. About half of all patients admitted to the NBU have burns to more than 11% of total body surface area (TBSA). The average stay in hospital was estimated to be 15.3 days per patient. The average in-hospital mortality rate was estimated to be 8.2% per year (range 1.9-22%)., Conclusion: Burns are significant public health issue in the Sultanate of Oman. Children are disproportionately over-represented in this study. Prevention programmes are urgently needed to address this "silent and costly epidemic.", (Copyright © 2013 Elsevier Ltd and ISBI. All rights reserved.)

There are two highly homologous survival motor neuron (SMN) genes in humans but molecular defects in the SMN1 gene cause spinal muscular atrophy (SMA). More than 90% of SMA patients are shown to have a homozygous deletion of exon 7 in the SMN1 gene. Therefore, a simple test for exon 7 deletion would be very useful in the molecular diagnosis of SMA. However, limited methods are available, and most of these methods utilize expensive instruments and consumables. Here, we describe a simple allele-specific PCR test, which can be performed using standard equipment in DNA laboratories. The principle of the test is based on a single nucleotide difference (C versus T) between the exon 7 of SMN1 and SMN2 genes. Using allele-specific primers, two PCR amplifications are performed for each sample to amplify a 404-bp diagnostic fragment, and consequent electrophoresis of PCR products on agarose gel provides definitive information concerning the exon 7 deletion To rule out false negatives, a 500-bp fragment from the N-acetyltransferase gene was coamplified as an internal control in each test. We have, so far, analyzed 41 SMA samples with our method, and tested the validity of results using an independent restriction fragment length polymorphism (RFLP) method. Genotyping results obtained by both methods were in complete agreement for all of the samples analyzed. Our method can also be used to detect heterozygous deletion of exon 7 in SMN genes, if the relative intensities of the diagnostic and internal control bands are determined.

We have investigated the prevalence of mutations in the connexin 26 (GJB2) gene in Omani population using both PCR-RFLP and direct DNA sequencing methods. Two common GJB2 gene mutations (35delG and 167delT) were screened in 280 healthy controls and 95 deaf patients using two different PCR-RFLP methods. To investigate other GJB2 mutations, we have amplified and sequenced DNA from 51 unrelated deaf patients and 17 control subjects. None of the samples studied, either by RFLP or sequencing, revealed any deafness-associated mutations in the coding region of the GJB2 gene. These findings disagree with many reports on the GJB2 gene, describing various mutations as the cause of congenital recessive deafness. Although, an amino acid substitution (S86T) was identified by sequencing, we conclude that this change could not be associated with deafness since it was present in all the control and patient samples sequenced., (Copyright 2001 Wiley-Liss, Inc.)