Systems Biology

Molecular Mechanisms of Resistance to Ionizing Radiation in <em>S. cerevisiae</em> and Its Relationship with Aging, Oxidative Stress, and Antioxidant Activity

Thu, 2023-09-28 06:00

Antioxidants (Basel). 2023 Aug 30;12(9):1690. doi: 10.3390/antiox12091690.

ABSTRACT

The repair of the damage produced to the genome and proteome by the action of ionizing radiation, oxidizing agents, and during aging is important to maintain cellular homeostasis. Many of the metabolic pathways influence multiple processes. In this way, this work aims to study the relationship between resistance/response to ionizing radiation, cellular aging, and the response mechanisms to oxidative stress, free radicals, reactive oxygen species (ROS), and antioxidant activity in the yeast S. cerevisiae. Systems biology allows us to use tools that reveal the molecular mechanisms common to different cellular response phenomena. The results found indicate that homologous recombination, non-homologous end joining, and base excision repair pathways are the most important common processes necessary to maintain cellular homeostasis. The metabolic routes of longevity regulation are those that jointly contribute to the three phenomena studied. This study proposes eleven common biomarkers for response/resistance to ionizing radiation and aging (EXO1, MEC1, MRE11, RAD27, RAD50, RAD51, RAD52, RAD55, RAD9, SGS1, YKU70) and two biomarkers for response/resistance to radiation and oxidative stress, free radicals, ROS, and antioxidant activity (NTG1, OGG1). In addition, it is important to highlight that the HSP104 protein could be a good biomarker common to the three phenomena studied.

PMID:37759994 | DOI:10.3390/antiox12091690

Categories: Literature Watch

Redox Metabolism and Vascular Calcification in Chronic Kidney Disease

Thu, 2023-09-28 06:00

Biomolecules. 2023 Sep 20;13(9):1419. doi: 10.3390/biom13091419.

ABSTRACT

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H2O2-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.

PMID:37759819 | DOI:10.3390/biom13091419

Categories: Literature Watch

Aptamer-Based Proteomics Measuring Preoperative Cerebrospinal Fluid Protein Alterations Associated with Postoperative Delirium

Thu, 2023-09-28 06:00

Biomolecules. 2023 Sep 15;13(9):1395. doi: 10.3390/biom13091395.

ABSTRACT

Delirium is a common postoperative complication among older patients with many adverse outcomes. Due to a lack of validated biomarkers, prediction and monitoring of delirium by biological testing is not currently feasible. Circulating proteins in cerebrospinal fluid (CSF) may reflect biological processes causing delirium. Our goal was to discover and investigate candidate protein biomarkers in preoperative CSF that were associated with the development of postoperative delirium in older surgical patients. We employed a nested case-control study design coupled with high multiplex affinity proteomics analysis to measure 1305 proteins in preoperative CSF. Twenty-four matched delirium cases and non-delirium controls were selected from the Healthier Postoperative Recovery (HiPOR) cohort, and the associations between preoperative protein levels and postoperative delirium were assessed using t-test statistics with further analysis by systems biology to elucidate delirium pathophysiology. Proteomics analysis identified 32 proteins in preoperative CSF that significantly associate with delirium (t-test p < 0.05). Due to the limited sample size, these proteins did not remain significant by multiple hypothesis testing using the Benjamini-Hochberg correction and q-value method. Three algorithms were applied to separate delirium cases from non-delirium controls. Hierarchical clustering classified 40/48 case-control samples correctly, and principal components analysis separated 43/48. The receiver operating characteristic curve yielded an area under the curve [95% confidence interval] of 0.91 [0.80-0.97]. Systems biology analysis identified several key pathways associated with risk of delirium: inflammation, immune cell migration, apoptosis, angiogenesis, synaptic depression and neuronal cell death. Proteomics analysis of preoperative CSF identified 32 proteins that might discriminate individuals who subsequently develop postoperative delirium from matched control samples. These proteins are potential candidate biomarkers for delirium and may play a role in its pathophysiology.

PMID:37759795 | DOI:10.3390/biom13091395

Categories: Literature Watch

Phylogenetic Analysis Guides Transporter Protein Deorphanization: A Case Study of the SLC25 Family of Mitochondrial Metabolite Transporters

Thu, 2023-09-28 06:00

Biomolecules. 2023 Aug 28;13(9):1314. doi: 10.3390/biom13091314.

ABSTRACT

Homology search and phylogenetic analysis have commonly been used to annotate gene function, although they are prone to error. We hypothesize that the power of homology search in functional annotation depends on the coupling of sequence variation to functional diversification, and we herein focus on the SoLute Carrier (SLC25) family of mitochondrial metabolite transporters to survey this coupling in a family-wide manner. The SLC25 family is the largest family of mitochondrial metabolite transporters in eukaryotes that translocate ligands of different chemical properties, ranging from nucleotides, amino acids, carboxylic acids and cofactors, presenting adequate experimentally validated functional diversification in ligand transport. Here, we combine phylogenetic analysis to profile SLC25 transporters across common eukaryotic model organisms, from Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, to Homo sapiens, and assess their sequence adaptations to the transported ligands within individual subfamilies. Using several recently studied and poorly characterized SLC25 transporters, we discuss the potentials and limitations of phylogenetic analysis in guiding functional characterization.

PMID:37759714 | DOI:10.3390/biom13091314

Categories: Literature Watch

Special Issue on Differential Gene Expression and Coexpression

Thu, 2023-09-28 06:00

Biology (Basel). 2023 Sep 11;12(9):1226. doi: 10.3390/biology12091226.

ABSTRACT

The most common approach in transcriptomics (RNA-seq and microarrays) is differential gene expression analysis (DGEA) [...].

PMID:37759625 | DOI:10.3390/biology12091226

Categories: Literature Watch

Integration of Omics Data and Network Models to Unveil Negative Aspects of SARS-CoV-2, from Pathogenic Mechanisms to Drug Repurposing

Thu, 2023-09-28 06:00

Biology (Basel). 2023 Aug 31;12(9):1196. doi: 10.3390/biology12091196.

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 health emergency, affecting and killing millions of people worldwide. Following SARS-CoV-2 infection, COVID-19 patients show a spectrum of symptoms ranging from asymptomatic to very severe manifestations. In particular, bronchial and pulmonary cells, involved at the initial stage, trigger a hyper-inflammation phase, damaging a wide range of organs, including the heart, brain, liver, intestine and kidney. Due to the urgent need for solutions to limit the virus' spread, most efforts were initially devoted to mapping outbreak trajectories and variant emergence, as well as to the rapid search for effective therapeutic strategies. Samples collected from hospitalized or dead COVID-19 patients from the early stages of pandemic have been analyzed over time, and to date they still represent an invaluable source of information to shed light on the molecular mechanisms underlying the organ/tissue damage, the knowledge of which could offer new opportunities for diagnostics and therapeutic designs. For these purposes, in combination with clinical data, omics profiles and network models play a key role providing a holistic view of the pathways, processes and functions most affected by viral infection. In fact, in addition to epidemiological purposes, networks are being increasingly adopted for the integration of multiomics data, and recently their use has expanded to the identification of drug targets or the repositioning of existing drugs. These topics will be covered here by exploring the landscape of SARS-CoV-2 survey-based studies using systems biology approaches derived from omics data, paying particular attention to those that have considered samples of human origin.

PMID:37759595 | DOI:10.3390/biology12091196

Categories: Literature Watch

Effect of Environmental Variables on African Penguin Vocal Activity: Implications for Acoustic Censusing

Thu, 2023-09-28 06:00

Biology (Basel). 2023 Aug 31;12(9):1191. doi: 10.3390/biology12091191.

ABSTRACT

Global biodiversity is in rapid decline, and many seabird species have disproportionally poorer conservation statuses than terrestrial birds. A good understanding of population dynamics is necessary for successful conservation efforts, making noninvasive, cost-effective monitoring tools essential. Here, we set out to investigate whether passive acoustic monitoring (PAM) could be used to estimate the number of animals within a set area of an African penguin (Spheniscus demersus) colony in South Africa. We were able to automate the detection of ecstatic display songs (EDSs) in our recordings, thus facilitating the handling of large datasets. This allowed us to show that calling rate increased with wind speed and humidity but decreased with temperature, and to highlight apparent abundance variations between nesting habitat types. We then showed that the number of EDSs in our recordings positively correlated with the number of callers counted during visual observations, indicating that the density could be estimated based on calling rate. Our observations suggest that increasing temperatures may adversely impact penguin calling behaviour, with potential negative consequences for population dynamics, suggesting the importance of effective conservation measures. Crucially, this study shows that PAM could be successfully used to monitor this endangered species' populations with minimal disturbance.

PMID:37759590 | DOI:10.3390/biology12091191

Categories: Literature Watch

Transcriptomic Analysis in the Hippocampus and Retina of Tg2576 AD Mice Reveals Defective Mitochondrial Oxidative Phosphorylation and Recovery by Tau 12A12mAb Treatment

Thu, 2023-09-28 06:00

Cells. 2023 Sep 12;12(18):2254. doi: 10.3390/cells12182254.

ABSTRACT

Increasing evidence implicates decreased energy metabolism and mitochondrial dysfunctions among the earliest pathogenic events of Alzheimer's disease (AD). However, the molecular mechanisms underlying bioenergetic dysfunctions in AD remain, to date, largely unknown. In this work, we analyzed transcriptomic changes occurring in the hippocampus and retina of a Tg2576 AD mouse model and wild-type controls, evaluating their functional implications by gene set enrichment analysis. The results revealed that oxidative phosphorylation and mitochondrial-related pathways are significantly down-regulated in both tissues of Tg2576 mice, supporting the role of these processes in the pathogenesis of AD. In addition, we also analyzed transcriptomic changes occurring in Tg2576 mice treated with the 12A12 monoclonal antibody that neutralizes an AD-relevant tau-derived neurotoxic peptide in vivo. Our analysis showed that the mitochondrial alterations observed in AD mice were significantly reverted by treatment with 12A12mAb, supporting bioenergetic pathways as key mediators of its in vivo neuroprotective and anti-amyloidogenic effects. This study provides, for the first time, a comprehensive characterization of molecular events underlying the disrupted mitochondrial bioenergetics in AD pathology, laying the foundation for the future development of diagnostic and therapeutic tools.

PMID:37759477 | DOI:10.3390/cells12182254

Categories: Literature Watch

Diverse Roles of Protein Palmitoylation in Cancer Progression, Immunity, Stemness, and Beyond

Thu, 2023-09-28 06:00

Cells. 2023 Sep 5;12(18):2209. doi: 10.3390/cells12182209.

ABSTRACT

Protein S-palmitoylation, a type of post-translational modification, refers to the reversible process of attachment of a fatty acyl chain-a 16-carbon palmitate acid-to the specific cysteine residues on target proteins. By adding the lipid chain to proteins, it increases the hydrophobicity of proteins and modulates protein stability, interaction with effector proteins, subcellular localization, and membrane trafficking. Palmitoylation is catalyzed by a group of zinc finger DHHC-containing proteins (ZDHHCs), whereas depalmitoylation is catalyzed by a family of acyl-protein thioesterases. Increasing numbers of oncoproteins and tumor suppressors have been identified to be palmitoylated, and palmitoylation is essential for their functions. Understanding how palmitoylation influences the function of individual proteins, the physiological roles of palmitoylation, and how dysregulated palmitoylation leads to pathological consequences are important drivers of current research in this research field. Further, due to the critical roles in modifying functions of oncoproteins and tumor suppressors, targeting palmitoylation has been used as a candidate therapeutic strategy for cancer treatment. Here, based on recent literatures, we discuss the progress of investigating roles of palmitoylation in regulating cancer progression, immune responses against cancer, and cancer stem cell properties.

PMID:37759431 | DOI:10.3390/cells12182209

Categories: Literature Watch

Artificial switches induce the bespoke production of functional compounds in marine microalgae Chlorella by neutralizing CO<sub>2</sub>

Wed, 2023-09-27 06:00

Biotechnol Biofuels Bioprod. 2023 Sep 27;16(1):143. doi: 10.1186/s13068-023-02381-5.

ABSTRACT

To improve the CO2 tolerance of a marine microalga Chlorella sp. of which the production capacity has been demonstrated industrially, a mutant library was created and a strain hct53 was screened. Compared to the parental strain, hct53 shows a high CO2 capture capacity, while starch biosynthesis is compromised, with increases in health beneficial metabolites and antioxidant capacity. Global gene expression and genome-wide mutation distribution revealed that transcript choreography was concomitant with more active CO2 sequestration, an increase in the lipid synthesis, and a decrease in the starch and protein synthesis. These results suggest that artificial trait improvement via mutagenesis, couple with multiomics analysis, helps discover genetic switches that induce the bespoke conversion of carbon flow from "redundant metabolites" to valuable ones for functional food.

PMID:37759320 | DOI:10.1186/s13068-023-02381-5

Categories: Literature Watch

Spatial atlas of the mouse central nervous system at molecular resolution

Wed, 2023-09-27 06:00

Nature. 2023 Sep 27. doi: 10.1038/s41586-023-06569-5. Online ahead of print.

ABSTRACT

Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain1,2, but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS3,4, to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm3, mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas1, imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB5,6. Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system.

PMID:37758947 | DOI:10.1038/s41586-023-06569-5

Categories: Literature Watch

A bioelectrical phase transition patterns the first vertebrate heartbeats

Wed, 2023-09-27 06:00

Nature. 2023 Sep 27. doi: 10.1038/s41586-023-06561-z. Online ahead of print.

ABSTRACT

A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart1-3, raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by CaV1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.

PMID:37758945 | DOI:10.1038/s41586-023-06561-z

Categories: Literature Watch

Methamphetamine-induced region-specific transcriptomic and epigenetic changes in the brain of male rats

Wed, 2023-09-27 06:00

Commun Biol. 2023 Sep 27;6(1):991. doi: 10.1038/s42003-023-05355-3.

ABSTRACT

Psychostimulant methamphetamine (METH) is neurotoxic to the brain and, therefore, its misuse leads to neurological and psychiatric disorders. The gene regulatory network (GRN) response to neurotoxic METH binge remains unclear in most brain regions. Here we examined the effects of binge METH on the GRN in the nucleus accumbens, dentate gyrus, Ammon's horn, and subventricular zone in male rats. At 24 h after METH, ~16% of genes displayed altered expression and over a quarter of previously open chromatin regions - parts of the genome where genes are typically active - showed shifts in their accessibility. Intriguingly, most changes were unique to each area studied, and independent regulation between transcriptome and chromatin accessibility was observed. Unexpectedly, METH differentially impacted gene activity and chromatin accessibility within the dentate gyrus and Ammon's horn. Around 70% of the affected chromatin-accessible regions in the rat brain have conserved DNA sequences in the human genome. These regions frequently act as enhancers, ramping up the activity of nearby genes, and contain mutations linked to various neurological conditions. By sketching out the gene regulatory networks associated with binge METH in specific brain regions, our study offers fresh insights into how METH can trigger profound, region-specific molecular shifts.

PMID:37758941 | DOI:10.1038/s42003-023-05355-3

Categories: Literature Watch

Monitoring saliva compositions for non-invasive detection of diabetes using a colorimetric-based multiple sensor

Wed, 2023-09-27 06:00

Sci Rep. 2023 Sep 27;13(1):16174. doi: 10.1038/s41598-023-43262-z.

ABSTRACT

The increasing population of diabetic patients, especially in developing countries, has posed a serious risk to the health sector, so that the lack of timely diagnosis and treatment process of diabetes can lead to threatening complications for the human lifestyle. Here, a multiple sensor was fabricated on a paper substrate for rapid detection and controlling the progress of the diabetes disease. The proposed sensor utilized the sensing ability of porphyrazines, pH-sensitive dyes and silver nanoparticles in order to detect the differences in saliva composition of diabetic and non-diabetic patients. A unique color map (sensor response) was obtained for each studied group, which can be monitored by a scanner. Moreover, a good correlation was observed between the colorimetric response resulting from the analysis of salivary composition and the fasting blood glucose (FBG) value measured by standard laboratory instruments. It was also possible to classify participants into two groups, including patients caused by diabetes and those were non-diabetic persons with a total accuracy of 88.9%. Statistical evaluations show that the multiple sensor can be employed as an effective and non-invasive device for continuous monitoring of diabetes, substantially in the elderly.

PMID:37758789 | DOI:10.1038/s41598-023-43262-z

Categories: Literature Watch

Genome-wide association studies identify loci controlling specialized seed metabolites in Arabidopsis

Wed, 2023-09-27 06:00

Plant Physiol. 2023 Sep 27:kiad511. doi: 10.1093/plphys/kiad511. Online ahead of print.

ABSTRACT

Plants synthesize specialized metabolites to facilitate environmental and ecological interactions. During evolution, plants diversified in their potential to synthesize these metabolites. Quantitative differences in metabolite levels of natural Arabidopsis (Arabidopsis thaliana) accessions can be employed to unravel the genetic basis for metabolic traits using genome-wide association studies (GWAS). Here, we performed metabolic GWAS (mGWAS) on seeds of a panel of 315 A. thaliana natural accessions, including the reference genotypes C24 and Col-0, for polar and semi-polar seed metabolites using untargeted ultra-performance liquid chromatography-mass spectrometry. As a complementary approach, we performed quantitative trait locus (QTL) mapping of near-isogenic introgression lines between C24 and Col-0 for specific seed specialized metabolites. Besides common QTL between seeds and leaves, GWAS revealed seed-specific QTL for specialized metabolites, indicating differences in the genetic architecture of seeds and leaves. In seeds, aliphatic methylsulfinylalkyl and methylthioalkyl glucosinolates associated with the ALKENYL HYDROXYALKYL PRODUCING loci (GS-ALK and GS-OHP) on chromosome 4 containing alkenyl hydroxyalkyl producing 2 (AOP2) and 3 (AOP3) or with the GS-ELONG locus on chromosome 5 containing methylthioalkyl malate synthase (MAM1) and MAM3. We detected two unknown sulfur-containing compounds that were also mapped to these loci. In GWAS, some of the annotated flavonoids (kaempferol 3-O-rhamnoside-7-O-rhamnoside, quercetin 3-O-rhamnoside-7-O-rhamnoside) were mapped to transparent testa 7 (AT5G07990), encoding a cytochrome P450 75B1 monooxygenase. Three additional mass signals corresponding to quercetin-containing flavonols were mapped to UGT78D2 (AT5G17050). The association of the loci and associating metabolic features were functionally verified in knockdown mutant lines. By performing GWAS and QTL mapping, we were able to leverage variation of natural populations and parental lines to study seed specialized metabolism. The GWAS dataset generated here is a high-quality resource that can be investigated in further studies.

PMID:37758174 | DOI:10.1093/plphys/kiad511

Categories: Literature Watch

Diagnostic accuracy of Tumor M2-Pyruvate Kinase (tM2-PK) as a non-invasive biomarker in colorectal cancer: A systematic review and meta-analysis

Wed, 2023-09-27 06:00

Clin Biochem. 2023 Sep 25:110652. doi: 10.1016/j.clinbiochem.2023.110652. Online ahead of print.

ABSTRACT

INTRODUCTION: The tumor pyruvate kinase M2 isoform (tM2-PK) is a glycolytic enzyme isoform that is present on the surface of rapidly proliferating cancer cells. The objective of this investigation was to assess the efficacy of the tM2-PK measurement assay in detecting colorectal cancer (CRC) through the analysis of serum/plasma and stool samples obtained from patients.

METHODS: The pooled diagnostic performance measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), the area under the curve (AUC), Q*index, and summary receiver-operating characteristiccurve (SROC), were computed using the Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.3.3 software. The statistical methods of I2 and chi-square were employed to assess the presence of heterogeneity. The estimation of publication bias was conducted through the implementation of Begg's rank correlation and Egger's regression asymmetry tests.

RESULTS: A total of 28 studies were found, involving 2900 participants (1560 cases and 1340 controls). The diagnostic accuracy of tM2-PK was calculated in CRC based on the pooled sensitivity of 83.70% (95% CI: 82.0% - 85.30%), specificity of 74.0% (95% CI: 72.0% - 76.0%), PLR of 4.432 (95% CI: 3.33 - 5.60), NLR of 0.187 (95% CI: 0.144 - 0.243), DOR of 30.182 (95% CI: 19.761 - 46.10) as well as AUC at 91.6%, and Q*-index at 85.0%. Publication bias was seen based on Begg's (p = 0.0006) and Egger's (p = 0.00015) tests.

CONCLUSION: The results demonstrate tM2-PK exhibits promise as a fair marker for CTRC, with the potential to serve as a non-invasive biomarker.

PMID:37757965 | DOI:10.1016/j.clinbiochem.2023.110652

Categories: Literature Watch

cfOmics: a cell-free multi-Omics database for diseases

Wed, 2023-09-27 06:00

Nucleic Acids Res. 2023 Sep 27:gkad777. doi: 10.1093/nar/gkad777. Online ahead of print.

ABSTRACT

Liquid biopsy has emerged as a promising non-invasive approach for detecting, monitoring diseases, and predicting their recurrence. However, the effective utilization of liquid biopsy data to identify reliable biomarkers for various cancers and other diseases requires further exploration. Here, we present cfOmics, a web-accessible database (https://cfomics.ncRNAlab.org/) that integrates comprehensive multi-omics liquid biopsy data, including cfDNA, cfRNA based on next-generation sequencing, and proteome, metabolome based on mass-spectrometry data. As the first multi-omics database in the field, cfOmics encompasses a total of 17 distinct data types and 13 specimen variations across 69 disease conditions, with a collection of 11345 samples. Moreover, cfOmics includes reported potential biomarkers for reference. To facilitate effective analysis and visualization of multi-omics data, cfOmics offers powerful functionalities to its users. These functionalities include browsing, profile visualization, the Integrative Genomic Viewer, and correlation analysis, all centered around genes, microbes, or end-motifs. The primary objective of cfOmics is to assist researchers in the field of liquid biopsy by providing comprehensive multi-omics data. This enables them to explore cell-free data and extract profound insights that can significantly impact disease diagnosis, treatment monitoring, and management.

PMID:37757861 | DOI:10.1093/nar/gkad777

Categories: Literature Watch

Activity of domain III-specific antibodies in early convalescence: A case study

Wed, 2023-09-27 06:00

Virology. 2023 Sep 15;587:109883. doi: 10.1016/j.virol.2023.109883. Online ahead of print.

ABSTRACT

The Dengue virus complex (DENV), formed by four serotypes, constitutes the most important arbovirus affecting humans. The structural domain III of their envelope protein (DIII) elicits strongly neutralizing serotype-specific antibodies. Contrasting results have been obtained regarding their role in the serum neutralizing activity of infected patients. We used a DENV immune serum from a secondary infection to examine the impact of characterizing the anti-DIII antibody response after affinity purification with recombinant DIII proteins to eliminate potential interferences from the interactions with human plasma proteins and other anti-DENV antibodies. Total anti-DENV IgG repertoire and anti-DIIIE antibodies were compared in functionality. In early convalescence, reactivity of anti-DIII antibodies is serotype specific and exhibits the strongest reactivity with infecting serotypes. Purification of anti-DIII antibodies emphasizes the reactivity profile as compared to total IgG fraction and serum. Serotype-specificity of the virus neutralization activity correlated with the apparent kD of the binding to recombinant DIIIs.

PMID:37757730 | DOI:10.1016/j.virol.2023.109883

Categories: Literature Watch

Insights into bacterial community metatranscriptome and metabolome in river water influenced by palm oil mill effluent final discharge

Wed, 2023-09-27 06:00

J Appl Microbiol. 2023 Sep 26:lxad219. doi: 10.1093/jambio/lxad219. Online ahead of print.

ABSTRACT

AIMS: This study aimed to investigate the effect of palm oil mill effluent (POME) final discharge on the active bacterial composition, gene expression, and metabolite profiles in the receiving rivers to establish a foundation for identifying potential biomarkers for monitoring POME pollution in rivers.

METHODS AND RESULTS: The POME final discharge, upstream (unpolluted by POME) and downstream (effluent receiving point) parts of the rivers from two sites were physicochemically characterised. The taxonomic and gene profiles were then evaluated using de novo metatranscriptomics, while the metabolites were detected using qualitative metabolomics. A similar bacterial community structure in the POME final discharge samples from both sites was recorded, but their composition varied. Redundancy analysis showed that several families, particularly Comamonadaceae and Burkholderiaceae (Pr(>F) = 0.028), were positively correlated with biochemical oxygen demand (BOD5) and chemical oxygen demand (COD). The results also showed significant enrichment of genes regulating various metabolisms in the POME-receiving rivers, with methane, carbon fixation pathway and amino acids among the predominant metabolisms identified (FDR < 0.05, PostFC > 4, PPDE > 0.95). This was further validated through qualitative metabolomics whereby amino acids were detected as the predominant metabolites.

CONCLUSIONS: The results suggest that genes regulating amino acid metabolism have significant potential for developing effective biomonitoring and bioremediation strategies in river water influenced by POME final discharge, fostering a sustainable palm oil industry.

PMID:37757470 | DOI:10.1093/jambio/lxad219

Categories: Literature Watch

Germline variant GFI1-36N affects DNA repair and sensitizes AML cells to DNA damage and repair therapy

Wed, 2023-09-27 06:00

Blood. 2023 Sep 26:blood.2022015752. doi: 10.1182/blood.2022015752. Online ahead of print.

ABSTRACT

Growth Factor Independence 1 (GFI1) is a DNA-binding transcription factor and a key regulator of haematopoiesis. GFI1-36N is a germline variant causing a change of serine (S) to asparagine (N) at position 36. We previously reported that the GFI1-36N allele has a prevalence of 10-15% among patients with acute myeloid leukemia (AML) and 5-7% among healthy Caucasians and promotes the development of this disease. Using a multi-omics approach, we show here that GFI1-36N expression is associated with increased frequencies of chromosomal aberrations, mutational burden and mutational signatures in both murine and human AML and impedes homologous recombination-directed (HR) DNA repair in leukemic cells. GFI1-36N exhibits impaired binding to N-Myc downstream-regulated gene 1 (Ndrg1) regulatory elements, causing decreased NDRG1 levels, which leads to a reduction of O6-methylguanine-DNA-methyltransferase (MGMT) expression levels illustrated by both transcriptome and proteome analyses. Targeting MGMT via temozolomide, a DNA alkylating drug, and HR via olaparib, a PARP1 inhibitor, caused synthetic lethality in human and murine AML samples expressing GFI1-36N, whereas the effects were insignificant in non-malignant GFI1-36S or GFI1-36N cells. In addition, mice transplanted with GFI1-36N leukemic cells treated with a combination of temozolomide and olaparib had significantly longer AML-free survival than mice transplanted with GFI1-36S leukemic cells. This suggests that reduced MGMT expression leaves GFI1-36N leukemic cells particularly vulnerable to DNA damage initiating chemotherapeutics. Our data provide critical insights into novel options to treat AML patients carrying the GFI1-36N variant.

PMID:37756525 | DOI:10.1182/blood.2022015752

Categories: Literature Watch

Pages