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Azathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant drugs. Polymorphisms in genes implicated in AZA/6-MP metabolism, reportedly, could account in part for their potential toxicity. In the present study we performed a systematic review and a meta-analysis, comprising 30 studies and 3582 individuals, to investigate the putative genetic association of two inosine triphosphatase (ITPA) polymorphisms with adverse effects in patients treated with AZA/6-MP. We found that rs1127354 is associated with neutropenia in general populations and in children (OR: 2.39, 95%CI: 1.97-2.90, and OR: 2.43, 95%CI: 2.12-2.79, respectively), and with all adverse effects tested herein in adult populations (OR: 2.12, 95%CI: 1.22-3.69). We also found that rs7270101 is associated with neutropenia and leucopenia in all-ages populations (OR: 2.93, 95%CI: 2.36-3.63, and OR: 2.82, 95%CI: 1.76-4.50, respectively) and with all adverse effects tested herein in children (OR: 1.74, 95%CI: 1.06-2.87). Stratification according to background disease, in combination with multiple comparisons corrections, verified neutropenia to be associated with both polymorphisms, in acute lymphoblastic leukemia (ALL) patients. These findings suggest that ITPA polymorphisms could be used as predictive biomarkers for adverse effects of thiopurine drugs to eliminate intolerance in ALL patients and clarify dosing in patients with different ITPA variants.
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Azatioprina/efectos adversos , Inmunosupresores/efectos adversos , Mercaptopurina/efectos adversos , Polimorfismo Genético/genética , Pirofosfatasas/genética , HumanosRESUMEN
OBJECTIVES: To provide a systematic review of the literature on studies comparing the immunoprofile of nevoid basal cell carcinoma syndrome (BCNS)-associated and sporadic odontogenic keratocysts (OKCs), in order to identify markers that could accurately distinguish the two OKC subtypes. MATERIALS AND METHODS: We searched MEDLINE/Pubmed, Web of Science, EMBASE via OVID, and grey literature for publications until December 28th, 2019, that compared the immunohistochemical expression of the two OKC subtypes. The studies were qualitatively assessed using the Critical Appraisal Tool for Case Series (Joana Briggs Institute). Sensitivity and specificity, positive and negative likelihood ratio, diagnostic odds ratio and area under the curve, and pooled estimates were calculated, using a random-effects model. RESULTS: Seventy-one studies were qualitatively analyzed; 61 markers were evaluated in one study and 32 in ≥ 2 studies. Twenty-five studies reported differential expression of 29 markers in the form of higher number of positive cells or greater staining intensity usually in BCNS-associated OKCs. Meta-analysis for bcl-2, Cyclin D1, CD56, CK18, p53, and PCNA showed that none of those markers is distinguishable between BCNS-associated and sporadic OKCs, in a 95% confidence interval. The risk of bias was high in 34 studies, moderate in 22, and low in 15. CONCLUSIONS: The present systematic review and meta-analysis uncovered that, although several immunohistochemical markers might characterize the OKC phenotype, they cannot discriminate between the BCNS-associated and sporadic OKCs. CLINICAL RELEVANCE: This study highlighted the requirement for additional screening for markers by immunohistochemistry, preferentially coupled to alternative diagnostic applications such as genomics technologies.
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Síndrome del Nevo Basocelular , Quistes Odontogénicos , Tumores Odontogénicos , Humanos , Inmunohistoquímica , Recurrencia Local de NeoplasiaRESUMEN
The use of high-dose Ionizing Radiation (IR) is currently one of the most common modalities in treatment of many types of cancer. The objective of this work was to investigate the effects of high-dose ionizing radiation on healthy human tissue, utilizing quantitative analysis of gene expression. To this end, publicly available transcriptomics datasets from human samples irradiated with a high dose of radiation and non-irradiated (control) ones were selected, and gene expression was determined using RNA-Seq data analysis. Raw data from these studies were subjected to quality control and trimming. Mapping of RNA-Seq reads was performed by the partial selective alignment method, and differential gene expression analysis was conducted. Subsequently, a meta-analysis was performed to select differentially expressed genes across datasets. Based on the differentially expressed genes discovered by meta-analysis, we constructed a protein-to-protein interaction network, and we identified biological pathways and processes related to high-dose IR effects. Our findings suggest that cell cycle arrest is activated, supported by our top down-regulated genes associated with cell cycle activation. DNA repair genes are down-regulated in their majority. However, several genes implicated in the nucleotide excision repair pathway are upregulated. Nevertheless, apoptotic mechanisms seem to be activated probably due to severe high-dose-induced complex DNA damage. The significant upregulation of CDKN1A, as a downstream gene of TP53, further validates programmed cell death. Finally, down-regulation of TIMELESS, signifies a correlation between IR response and circadian rhythm. Nonetheless, high-dose IR exposure effects regarding normal tissue (radiation toxicity) and its possible long-term outcomes should be studied to a greater extend.
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Expresión Génica/efectos de la radiación , Radiación Ionizante , Puntos de Control del Ciclo Celular/efectos de la radiación , Daño del ADN/efectos de la radiación , Reparación del ADN/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Regulación hacia Abajo/efectos de la radiación , Perfilación de la Expresión Génica/métodos , Humanos , Regulación hacia Arriba/efectos de la radiaciónRESUMEN
Introduction Impaired perceptual organisation in schizophrenia has been repeatedly described in clinical and research literatures. It has also been associated with problems in more complex aspects of visual function, including visuospatial and visual cognitive test performance. Two therapeutic interventions were developed here that target perceptual organisation: (1) Computer-based training, which emphasized stimulus-driven processing (bottom-up approach), and (2) Instrumental Enrichment therapy, which is a therapist-guided interactive learning method (top-down approach). Methods Twenty-eight patients diagnosed with schizophrenia or schizoaffective disorder participated in a 12-week programme. For both forms of interventions, task difficulty increased progressively, based upon successful performance. The third group of patients, which served as controls, received a similar therapeutic intervention that did not include a perceptual organisation component. Before and after intervention, participants received tests of perceptual organisation, as well as a battery of neuropsychological tests. Results Results indicate that both forms of intervention improved perceptual organisation ability relative to the control condition. In addition, the improvement was found for select neuropsychological tests, although the pattern of improvement did not favour capacities more closely associated with visual organisational or visuospatial function. Conclusions Together, results demonstrate the effectiveness of new remediation protocols that target mid-level visual processing, which generalized to select visual cognitive functions.
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Psicoterapia/métodos , Esquizofrenia/terapia , Psicología del Esquizofrénico , Percepción Espacial , Percepción Visual , Adulto , Cognición , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Esquizofrenia/diagnóstico , Resultado del TratamientoRESUMEN
MicroRNAs are small, non-coding RNAs which regulate post-transcriptionally hundreds of target mRNAs. Given that their expression is deregulated in several cancer types, they represent potential diagnostic, prognostic, and predictive biomarkers, as well as next-generation therapeutic targets. Nevertheless, the involvement of miRNAs in non-melanoma skin cancer, a cancer type with increasing prevalence, is not extensively studied, and their comprehensive characterization as regard to the initiation, promotion, and progression stages is missing. To this end, we exploited a well-established multistage mouse skin carcinogenesis model in order to identify miRNAs consistently implicated in different stages of skin carcinogenesis. The cell lines comprising this model were subjected to miRNA expression profiling using microarrays, followed by bioinformatics analysis and validation with Q-PCR, as well as treatment with miRNA modulators. We showed that among all deregulated miRNAs in our system, only a functionally coherent group consisting of the miR-200 family members and miR-205-5p displays a pattern of progressive co-downregulation from the early toward the most aggressive stages of carcinogenesis. Their overlapping, co-regulated putative targets are potentially inter-associated and, of these, the EMT-related Rap1a is overexpressed toward aggressive stages. Ectopic expression of miR-205-5p in spindle cancer cells reduces Rap1a, mitigates cell invasiveness, decreases proliferation, and delays tumor onset. We conclude that deregulation of this miRNA group is primarily associated with aggressive phenotypes of skin cancer cells. Restoration of the miR-205-5p member of this group in spindle cells reduces the expression of critical, co-regulated targets that favor cancer progression, thus reversing the EMT characteristics. © 2015 Wiley Periodicals, Inc.
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Perfilación de la Expresión Génica/métodos , MicroARNs/genética , Análisis de Secuencia por Matrices de Oligonucleótidos/métodos , Neoplasias Cutáneas/patología , Proteínas de Unión al GTP rap1/genética , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Progresión de la Enfermedad , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Trasplante de Neoplasias , Neoplasias Cutáneas/genéticaRESUMEN
Common fragile sites (CFSs) are regions of the genome with a predisposition to DNA double-strand breaks in response to intrinsic (oncogenic) or extrinsic replication stress. CFS breakage is a common feature in carcinogenesis from its earliest stages. Given that a number of oncogenes and tumor suppressors are located within CFSs, a question that emerges is whether fragility in these regions is only a structural "passive" incident or an event with a profound biological effect. Furthermore, there is sparse evidence that other elements, like non-coding RNAs, are positioned with them. By analyzing data from various libraries, like miRbase and ENCODE, we show a prevalence of various cancer-related genes, miRNAs, and regulatory binding sites, such as CTCF within CFSs. We propose that CFSs are not only susceptible structural domains, but highly organized "functional" entities that when targeted, severe repercussion for cell homeostasis occurs.
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Sitios Frágiles del Cromosoma , Neoplasias/genética , Oncogenes , Animales , Reparación del ADN , Replicación del ADN , Humanos , MicroARNs/genéticaRESUMEN
Allicin is a thiosulphate molecule produced in garlic (Allium sativum) and has a wide range of biological actions and pharmaceutical applications. Its precursor molecule is the non-proteinogenic amino acid alliin (S-allylcysteine sulphoxide). The alliin biosynthetic pathway in garlic involves a group of enzymes, members of which are the γ-glutamyl-transpeptidase isoenzymes, Allium sativum γ-glutamyl-transpeptidase AsGGT1, AsGGT2 and AsGGT3, which catalyze the removal of the γ-glutamyl group from γ-glutamyl-S-allyl-L-cysteine to produce S-allyl-L-cysteine. This removal is followed by an S-oxygenation, which leads to the biosynthesis of alliin. The aim of the present study is to annotate previously discovered genes of garlic γ-glutamyl-transpeptidases, as well as a fourth candidate gene (AsGGT4) that has yet not been described. The annotation includes identifying the loci of the genes in the garlic genome, revealing the overall structure and conserved regions of these genes, and elucidating the evolutionary history of these enzymes through their phylogenetic analysis. The genomic structure of γ-glutamyl-transpeptidase genes is conserved; each gene consists of seven exons, and these genes are located on different chromosomes. AsGGT3 and AsGGT4 enzymes contain a signal peptide. To that end, the AsGGT3 protein sequence was corrected; four indel events occurring in AsGGT3 coding regions suggested that at least in the garlic variety Ershuizao, AsGGT3 may be a pseudogene. Finally, the use of protein structure prediction tools allowed the visualization of the tertiary structure of the candidate peptide.
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Head and neck squamous cell carcinomas (HNSCCs), a heterogeneous group of cancers that arise from the mucosal epithelia cells in the head and neck areas, present great challenges in diagnosis, treatment and prognosis due to their complex aetiology and various clinical manifestations. Several factors, including smoking, alcohol consumption, oncogenic genes, growth factors, EpsteinBarr virus and human papillomavirus infections can contribute to HNSCC development. The unpredictable tumour microenvironment adds to the complexity of managing HNSCC. Despite significant advances in therapies, the prediction of outcome after treatment for patients with HNSCC remains poor, and the 5year overall survival rate is low due to late diagnosis. Early detection greatly increases the chances of successful treatment. The present review aimed to bring together the latest findings related to the molecular mechanisms of HNSCC carcinogenesis and progression. Comprehensive genomic, transcriptomic, metabolomic, microbiome and proteomic analyses allow researchers to identify important biological markers such as genetic alterations, gene expression signatures and protein markers that drive HNSCC tumours. These biomarkers associated with the stages of initiation, progression and metastasis of cancer are useful in the management of patients with cancer in order to improve their life expectancy and quality of life.
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Neoplasias de Cabeza y Cuello , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Microambiente Tumoral , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/virología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinogénesis/genética , Pronóstico , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/patologíaRESUMEN
During future space missions, astronauts will be exposed to cosmic radiation and microgravity (µG), which are known to be health risk factors. To examine the differentially expressed genes (DEG) and their prevalent biological processes and pathways as a response to these two risk factors simultaneously, 1BR-hTERT human fibroblast cells were cultured under 1 gravity (1G) or simulated µG for 48 h in total and collected at 0 (sham irradiated), 3 or 24 h after 1 Gy of X-ray or Carbon-ion (C-ion) irradiation. A three-dimensional clinostat was used for the simulation of µG and the simultaneous radiation exposure of the samples. The RNA-seq method was used to produce lists of differentially expressed genes between different environmental conditions. Over-representation analyses were performed and the enriched biological pathways and targeting transcription factors were identified. Comparing sham-irradiated cells under simulated µG and 1G conditions, terms related to response to oxygen levels and muscle contraction were identified. After irradiation with X-rays or C-ions under 1G, identified DEGs were found to be involved in DNA damage repair, signal transduction by p53 class mediator, cell cycle arrest and apoptosis pathways. The same enriched pathways emerged when cells were irradiated under simulated µG condition. Nevertheless, the combined effect attenuated the transcriptional response to irradiation which may pose a subtle risk in space flights.
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Ingravidez , Humanos , Ingravidez/efectos adversos , Radiación Ionizante , Fibroblastos , Simulación por Computador , Expresión GénicaRESUMEN
Predictive tools provide a unique opportunity to explain the observed differences in outcome between patients of the COVID-19 pandemic. The aim of this study was to associate individual demographic and clinical characteristics with disease severity in COVID-19 patients and to highlight the importance of machine learning (ML) in disease prognosis. The study enrolled 344 unvaccinated patients with confirmed SARS-CoV-2 infection. Data collected by integrating questionnaires and medical records were imported into various classification machine learning algorithms, and the algorithm and the hyperparameters with the greatest predictive ability were selected for use in a disease outcome prediction web tool. Of 111 independent features, age, sex, hypertension, obesity, and cancer comorbidity were found to be associated with severe COVID-19. Our prognostic tool can contribute to a successful therapeutic approach via personalized treatment. Although at the present time vaccination is not considered mandatory, this algorithm could encourage vulnerable groups to be vaccinated.
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The most common approach in transcriptomics (RNA-seq and microarrays) is differential gene expression analysis (DGEA) [...].
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Removal of the 5' cap structure of RNAs (termed decapping) is a pivotal event in the life of cytoplasmic mRNAs mainly catalyzed by a conserved holoenzyme, composed of the catalytic subunit DCP2 and its essential cofactor DCP1. While decapping was initially considered merely a step in the general 5'-3' mRNA decay, recent data suggest a great degree of selectivity that plays an active role in the post-transcriptional control of gene expression, and regulates multiple biological functions. Studies in Caenorhabditis elegans have shown that old age is accompanied by the accumulation of decapping factors in cytoplasmic RNA granules, and loss of decapping activity shortens the lifespan. However, the link between decapping and ageing remains elusive. Here, we present a comparative microarray study that was aimed to uncover the differences in the transcriptome of mid-aged dcap-1/DCP1 mutant and wild-type nematodes. Our data indicate that DCAP-1 mediates the silencing of spermatogenic genes during late oogenesis, and suppresses the aberrant uprise of immunity gene expression during ageing. The latter is achieved by destabilizing the mRNA that encodes the transcription factor PQM-1 and impairing its nuclear translocation. Failure to exert decapping-mediated control on PQM-1 has a negative impact on the lifespan, but mitigates the toxic effects of polyglutamine expression that are involved in human disease.
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The discovery of therapeutic miRNAs is one of the most exciting challenges for pharmaceutical companies. Since the first miRNA was discovered in 1993, our knowledge of miRNA biology has grown considerably. Many studies have demonstrated that miRNA expression is dysregulated in many diseases, making them appealing tools for novel therapeutic approaches. This review aims to discuss miRNA biogenesis and function, as well as highlight strategies for delivering miRNA agents, presenting viral, non-viral, and exosomic delivery as therapeutic approaches for different cancer types. We also consider the therapeutic role of microRNA-mediated drug repurposing in cancer therapy.
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BACKGROUND: Stem cells have been associated with self-renewing and plasticity and have been investigated in various odontogenic lesions in association with their pathogenesis and biological behavior. We aim to provide a systematic review of stem cell markers' expression in odontogenic tumors and cysts. METHODS: The literature was searched through the MEDLINE/PubMed, EMBASE via OVID, Web of Science, and CINHAL via EBSCO databases for original studies evaluating stem cell markers' expression in different odontogenic tumors/cysts, or an odontogenic disease group and a control group. The studies' risk of bias (RoB) was assessed via a Joanna Briggs Institute Critical Appraisal Tool. Meta-analysis was conducted for markers evaluated in the same pair of odontogenic tumors/cysts in at least two studies. RESULTS: 29 studies reported the expression of stem cell markers, e.g., SOX2, OCT4, NANOG, CD44, ALDH1, BMI1, and CD105, in various odontogenic lesions, through immunohistochemistry/immunofluorescence, polymerase chain reaction, flow cytometry, microarrays, and RNA-sequencing. Low, moderate, and high RoBs were observed in seven, nine, and thirteen studies, respectively. Meta-analysis revealed a remarkable discriminative ability of SOX2 for ameloblastic carcinomas or odontogenic keratocysts over ameloblastomas. CONCLUSION: Stem cells might be linked to the pathogenesis and clinical behavior of odontogenic pathologies and represent a potential target for future individualized therapies.
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Genes with similar expression patterns in a set of diverse samples may be considered coexpressed. Human Gene Coexpression Analysis 2.0 (HGCA2.0) is a webtool which studies the global coexpression landscape of human genes. The website is based on the hierarchical clustering of 55,431 Homo sapiens genes based on a large-scale coexpression analysis of 3500 GTEx bulk RNA-Seq samples of healthy individuals, which were selected as the best representative samples of each tissue type. HGCA2.0 presents subclades of coexpressed genes to a gene of interest, and performs various built-in gene term enrichment analyses on the coexpressed genes, including gene ontologies, biological pathways, protein families, and diseases, while also being unique in revealing enriched transcription factors driving coexpression. HGCA2.0 has been successful in identifying not only genes with ubiquitous expression patterns, but also tissue-specific genes. Benchmarking showed that HGCA2.0 belongs to the top performing coexpression webtools, as shown by STRING analysis. HGCA2.0 creates working hypotheses for the discovery of gene partners or common biological processes that can be experimentally validated. It offers a simple and intuitive website design and user interface, as well as an API endpoint.
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Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Genes , Humanos , RNA-Seq , Factores de Transcripción , Genes/genética , Genes/fisiologíaRESUMEN
Coexpressed genes tend to participate in related biological processes. Gene coexpression analysis allows the discovery of functional gene partners or the assignment of biological roles to genes of unknown function. In this protocol, we describe the steps necessary to create a gene coexpression tree for Arabidopsis thaliana, using publicly available Affymetrix CEL microarray data. Because the computational analysis described here is highly dependent on sample quality, we detail an automatic quality control approach. For complete details on the use and execution of this protocol, please refer to Zogopoulos et al. (2021).
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Perfilación de la Expresión Génica/métodos , Pruebas Genéticas , Análisis de Secuencia por Matrices de Oligonucleótidos/métodosRESUMEN
Gene coexpression analysis constitutes a widely used practice for gene partner identification and gene function prediction, consisting of many intricate procedures. The analysis begins with the collection of primary transcriptomic data and their preprocessing, continues with the calculation of the similarity between genes based on their expression values in the selected sample dataset and results in the construction and visualisation of a gene coexpression network (GCN) and its evaluation using biological term enrichment analysis. As gene coexpression analysis has been studied extensively, we present most parts of the methodology in a clear manner and the reasoning behind the selection of some of the techniques. In this review, we offer a comprehensive and comprehensible account of the steps required for performing a complete gene coexpression analysis in eukaryotic organisms. We comment on the use of RNA-Seq vs. microarrays, as well as the best practices for GCN construction. Furthermore, we recount the most popular webtools and standalone applications performing gene coexpression analysis, with details on their methods, features and outputs.
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BACKGROUND: Age at onset is one of the most critical factors contributing to the clinical heterogeneity of Parkinson's disease (PD), and available evidence is rather conflicting. OBJECTIVE: The aim of this study is to investigate the clinical differences between early-onset PD (EOPD) and mid-and-late-onset PD (MLOPD) in the Greek population, based on the existing data of the Hellenic Biobank of PD (HBPD). METHODS: HBPD contains information of PD cases from two centers in Greece during 2006-2017. Patients with the A53T mutation in the SNCA gene or mutations in the GBA1 gene were excluded. Associations between clinical characteristics (motor and non-motor symptoms, side of onset, first symptom, motor complications) and MLOPD versus EOPD were explored with a single logistic regression model adjusting for gender, family history of PD, disease and dopaminergic therapy duration, disease severity (UPDRS III), levodopa equivalent daily dose, as well as each of the other clinical characteristics. RESULTS: 675 patients (129 EOPD, 546 MLOPD) were included. EOPD was more frequently associated with dystonia (OR 0.19, 95% CI 0.08-0.50, p < 0.01) and motor complications (0.23, 0.07-0.76, 0.02), compared to MLOPD. Bilateral onset (9.38, 1.05-84.04, 0.045) and autonomic dysfunction (2.31, 1.04-5.11, 0.04) were more frequently associated with MLOPD. CONCLUSIONS: EOPD and MLOPD display distinct clinical profiles, regarding motor and non-motor symptoms, side of onset and motor complications in the Greek population. These differences may reflect diverse pathophysiological backgrounds, potentially attributed to genetic or age-related epigenetic influences.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/complicaciones , Levodopa/uso terapéutico , Análisis de Datos , Bancos de Muestras Biológicas , Edad de Inicio , Enfermedades de Inicio Tardío/complicacionesRESUMEN
Genome assemblers are computational tools for de novo genome assembly, based on a plenitude of primary sequencing data. The quality of genome assemblies is estimated by their contiguity and the occurrences of misassemblies (duplications, deletions, translocations or inversions). The rapid development of sequencing technologies has enabled the rise of novel de novo genome assembly strategies. The ultimate goal of such strategies is to utilise the features of each sequencing platform in order to address the existing weaknesses of each sequencing type and compose a complete and correct genome map. In the present study, the hybrid strategy, which is based on Illumina short pairedend reads and Nanopore long reads, was benchmarked using MaSuRCA and Wengan assemblers. Moreover, the longread assembly strategy, which is based on Nanopore reads, was benchmarked using Canu or PacBio HiFi reads were benchmarked using Hifiasm and HiCanu. The assemblies were performed on a computational cluster with limited computational resources. Their outputs were evaluated in terms of accuracy and computational performance. PacBio HiFi assembly strategy outperforms the other ones, while HiC scaffolding, which is based on chromatin 3D structure, is required in order to increase continuity, accuracy and completeness when large and complex genomes, such as the human one, are assembled. The use of HiC data is also necessary while using the hybrid assembly strategy. The results revealed that HiFi sequencing enabled the rise of novel algorithms which require less genome coverage than that of the other strategies making the assembly a less computationally demanding task. Taken together, these developments may lead to the democratisation of genome assembly projects which are now approachable by smaller labs with limited technical and financial resources.
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Algoritmos , Genoma Humano , Genoma de los Insectos , Secuenciación de Nucleótidos de Alto Rendimiento , Animales , Benchmarking , Drosophila melanogaster , HumanosRESUMEN
The use of high linear energy transfer (LET) ionizing radiation (IR) is progressively being incorporated in radiation therapy due to its precise dose localization and high relative biological effectiveness. At the same time, these benefits of particle radiation become a high risk for astronauts in the case of inevitable cosmic radiation exposure. Nonetheless, DNA Damage Response (DDR) activated via complex DNA damage in healthy tissue, occurring from such types of radiation, may be instrumental in the induction of various chronic and late effects. An approach to elucidating the possible underlying mechanisms is studying alterations in gene expression. To this end, we identified differentially expressed genes (DEGs) in high Z and high energy (HZE) particle-, γ-ray- and X-ray-exposed healthy human tissues, utilizing microarray data available in public repositories. Differential gene expression analysis (DGEA) was conducted using the R programming language. Consequently, four separate meta-analyses were conducted, after DEG lists were grouped depending on radiation type, radiation dose and time of collection post-irradiation. To highlight the biological background of each meta-analysis group, functional enrichment analysis and biological network construction were conducted. For HZE particle exposure at 8-24 h post-irradiation, the most interesting finding is the variety of DNA repair mechanisms that were downregulated, a fact that is probably correlated with complex DNA damage formation. Simultaneously, after X-ray exposure during the same hours after irradiation, DNA repair mechanisms continue to take place. Finally, in a further comparison of low- and high-LET radiation effects, the most prominent result is that autophagy mechanisms seem to persist and that adaptive immune induction seems to be present. Such bioinformatics approaches may aid in obtaining an overview of the cellular response to high-LET particles. Understanding these response mechanisms can consequently aid in the development of countermeasures for future space missions and ameliorate heavy ion treatments.