Biology subjects

Arif, M.

Publications and source records attributed to Arif, M..

34 records · Page 2Linked to original sources

bioRxiv2022

Elevation of Clavibacter michiganensis subsp. californiensis to species level as Clavibacter californiensis sp. nov., merging and re-classification of Clavibacter michiganensis subsp. chilensis and Clavibacter michiganensis subsp. phaseoli as Clavibacter chilensis sp. nov. based on complete genome in-silico analyses

The Gram-positive Clavibacter genus is currently divided into seven species (C. michiganensis, C. nebraskensis, C. capsici, C. sepedonicus, C. tessellarius, C. insidiosus and C. zhangzhiyongii) and three subspecies (C. michiganensis subsp. californiensis, C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli). Recent studies have indicated that the taxonomic rank of the subspecies must be re-evaluated. In this research, we assessed the taxonomy position of the three C. michiganensis subspecies and clarified the taxonomic nomenclature of other 75 Clavibacter strains. The complete genomes of the type strains of the three Clavibacter subspecies, type strain of C. tessellarius and C. nebraskensis A6096 were sequenced using PacBio RSII technology. Application of whole-genome-based computational approaches such as average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), multi-locus sequence analysis (MLSA) of seven housekeeping genes (acnA, atpD, bipA, icdA, mtlD, recA and rpoB), phylogenomic tree reconstructed from 1,028 core genes, and ANI-based phylogeny pinpointed conclusive evidence to raise C. michiganensis subsp. californiensis to the species status. These results led us to propose the establishment of C. californiensis sp. nov. as a species with its type strain C55 (=CFBP 8216=ATCC BAA-2691). Moreover, the orthologous and in-silico dot plot analyses, along with the aforementioned bioinformatic strategies, revealed a high degree of homology between C. michiganensis subsp. chilensis and C. michiganensis subsp. phaseoli. Based on these outcomes, we proposed to combine both subspecies into a single taxon and elevate its rank to the species level as C. chilensis sp. nov., with ZUM3936 (= ATCC BAA-2690 = CFBP 8217) as the type strain.

microbiology↗

bioRxiv2022

Dickeya colocasiae sp. nov. isolated from wetland taro, Colocasia esculentum

Bacterial pathogens identified as Dickeya sp. have recently been associated with a corm rot of wetland taro on Oahu, Hawaii, but the species designation of these strains was unclear. A Gram-negative, pectinolytic bacterial strain PL65T isolated from an infected taro corm was subjected to polyphasic analysis to determine its genomic and phenotypic characteristics. Multi-locus sequence analyses (MLSA) based on five housekeeping genes (dnaA, gapA, gyrB, atpD, and purA) revealed that Dickeya zeae and D. oryzae, were the closest relatives. Phylogenetic analysis based on 463 core gene sequences clearly showed two potentially new species within Dickeya oryzae. In silico DNA- DNA hybridization value of strain PL65T with 12 Type strains of Dickeya species was <68%. Average nucleotide identity (ANI) analysis revealed that PL65T was at the margin of the species delineation cut-off values with a 96% ANI value. The metabolic profile of strain PL65T using BIOLOG differentiated it from the type strains of all other known species of Dickeya. Based on the results of genome-to-genome comparisons and phenotypic data presented in this report, we propose establishment of a new species, Dickeya colocasiae sp. nov. with strain PL65T as the type strain (ICMP 24361T).

microbiology↗

bioRxiv2021

GutMicroNet: an interactive platform for gut microbiome interaction exploration

The human gut microbiome data has been proven to be a powerful tool to understand the human body in both health and disease conditions. However, understanding their complex interactions and impact on the human body remains a challenging task. Unravelling the species-level interactions could allow us to study the causality of the microbiome. Moreover, it could lead us to better understand the underlying mechanisms of complex diseases and, subsequently, the discovery of new therapeutic targets. Given these challenges and benefits, it has become evident that a freely accessible and centralized platform for presenting gut microbiome interaction is essential to untangle the complexity and open multiple new paths and opportunities in disease- and drug-related research. Here, we present GutMicroNet, an interactive visualization platform of human gut microbiome interaction networks. We generated 45 gut microbiome co-abundance networks from various geographical origins, gender, and diseases based on the data presented in the Human Gut Microbiome Atlas. This interactive platform includes more than 1900 gut microbiome species and allows users to query multiple species at the same time based on their interests and adjust it based on the statistical properties. Moreover, users can download publication-ready figures or network information for further analysis. The platform can be accessed freely on https://gutmicro.net without any login requirements or limitations, including access to the full networks data.

systems biology↗

bioRxiv2021

A network-based approach reveals the dysregulated transcriptional regulation in non-alcohol fatty liver disease

Non-alcohol-related fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. We performed network analysis to investigate the dysregulated biological processes in the disease progression and revealed the molecular mechanism underlying NAFLD. Based on network analysis, we identified a highly conserved disease-associated gene module across three different NAFLD cohorts and highlighted the predominant role of key transcriptional regulators associated with lipid and cholesterol metabolism. In addition, we revealed the detailed metabolic differences between heterogenous NAFLD patients through integrative systems analysis of transcriptomic data and liver-specific genome-scale metabolic model. Furthermore, we identified transcription factors (TFs), including SREBF2, HNF4A, SREBF1, YY1 and KLF13, showing regulation of hepatic expression of genes in the NAFLD-associated modules and validated the TFs using data generated from a mouse NAFLD model. In conclusion, our integrative analysis facilitated our understanding of the regulatory mechanism of these perturbed TFs and associated biological processes.

systems biology↗

bioRxiv2021

Systems analysis reveals ageing-related perturbations in retinoids and sex hormones in Alzheimer's and Parkinson's diseases

Neurodegenerative diseases (NDDs), including Alzheimers (AD) and Parkinsons diseases (PD), are complex heterogeneous diseases with highly variable patient responses to treatment. Due to the growing evidence for ageing-related clinical and pathological commonalities between AD and PD, these diseases have recently been studied in tandem. In this study, we analyse transcriptomic data from AD and PD patients, and stratify these patients into three subclasses with distinct gene expression and metabolic profiles. Through integrating transcriptomic data with a genome-scale metabolic model and validating our findings by network exploration and co-analysis using a zebrafish ageing model, we identify retinoids as a key ageing-related feature in all subclasses of AD and PD. We also demonstrate that the dysregulation of androgen metabolism by three different independent mechanisms is a source of heterogeneity in AD and PD. Taken together, our work highlights the need for stratification of AD/PD patients and development of personalised and precision medicine approaches based on the detailed characterisation of these subclasses.

systems biology↗

bioRxiv2021

Orc6 at replication fork enables efficient mismatch repair

In eukaryotes, the Origin Recognition Complex (ORC) is required for the initiation of DNA replication. The smallest subunit of ORC, Orc6, is essential for pre-replication complex (pre-RC) assembly and cell viability in yeast and for cytokinesis in metazoans. However, unlike other ORC components, the role of human Orc6 in replication remains to be resolved. Here, we identify an unexpected role for hOrc6, which is to promote S-phase progression post pre-RC assembly and DNA damage response. Orc6 localizes at the replication fork and is an accessory factor of the mismatch repair (MMR) complex. In response to oxidative damage during S-phase, often repaired by MMR, Orc6 facilitates MMR complex assembly and activity, without which the checkpoint signaling is abrogated. Mechanistically, Orc6 directly binds to MutS and enhances the chromatin-association of MutL, thus enabling efficient mismatch repair. Based on this, we conclude that hOrc6 plays a fundamental role in genome surveillance during S-phase. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/443400v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@bfdaa8org.highwire.dtl.DTLVardef@1ac791dorg.highwire.dtl.DTLVardef@436d1corg.highwire.dtl.DTLVardef@b07689_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHuman Orc6 is dispensable for G1 licensing, but required for S-phase progression C_LIO_LIHuman Orc6 at the replication fork is an accessory factor for MMR complex C_LIO_LIDepletion of hOrc6 sensitizes cells to DNA damage and impairs ATR activation C_LIO_LIHuman Orc6 regulates MMR complex assembly and activity C_LI

molecular biology↗

bioRxiv2021

Genomic and phenotypic biology of novel strains of Dickeya zeae isolated from pineapple and taro in Hawaii: insights into genome plasticity, pathogenicity, and virulence determinants

Dickeya zeae, a bacterial plant pathogen in the family Pectobacteriaceae, is responsible for a wide range of diseases on potato, maize, rice, banana, pineapple, taro and ornamentals and significantly reduces crop production; D. zeae causes soft rot of taro (Colocasia esculenta) and heart rot of pineapple (Ananas comosus). In this study, we used Pacific Biosciences to sequence two high quality complete genomes of novel strains of D. zeae: PL65 (size - 4.74997 MB; depth - 701; GC - 53.3%) and A5410 (size - 4.7792 MB; depth - 558; GC - 53.6%) isolated from economically important Hawaiian crops, taro and pineapple, respectively. Additional complete genomes of D. zeae representing two additional hosts (rice and banana), and other species for taxonomic comparison, were retrieved from the NCBI GenBank genome database. The genomic analyses indicated truncated type III and IV secretion systems (T3SS and T4SS) in the taro strain, which only harbors 1 and 2 genes of T3SS and T4SS, respectively, and showed high heterogeneity in the type VI secretion system. Unlike the EC1 strain, neither the PL65 nor the A5410 genome harbors the zeamine biosynthesis gene cluster, which plays a key role in bacterial virulence. The ANI and dDDH percentages between the two genomes were 94.47 and 57.00, respectively. In this study, we compared major virulence factors (plant cell wall-degrading extracellular enzymes and protease) produced by D. zeae strains and virulence ability on taro corms and pineapple. Both strains produced protease, pectate lyases and cellulases but no significant quantitative differences were observed (p>0.05) among the strains. All the strains produced symptoms on taro corms and pineapple leaves. Strain PL65 developed symptoms faster than the others. Our study highlights genetic constituents of pathogenicity determinants and genomic heterogeneity that will help understand the virulence mechanisms and aggressiveness of this plant pathogen.

genomics↗

bioRxiv2020

Revealing tissue-specific metabolic crosstalk after a myocardial infarction

Abstract/SummaryMyocardial infarction (MI) promotes a range of systemic effects, many of which are unknown. Here, we investigated the alterations associated with MI progression in heart and other metabolically active tissues (liver, skeletal muscle, and adipose) in a mouse model of MI (induced by ligating the left ascending coronary artery) and sham-operated mice. We performed a genome-wide transcriptomic analysis on tissue samples obtained 6- and 24-hours post MI or sham operation. By generating tissue-specific biological networks, we observed: (1) dysregulation in multiple biological processes (including immune system, mitochondrial dysfunction, fatty-acid beta-oxidation, and RNA and protein processing) across multiple tissues post MI; and (2) tissue-specific dysregulation in biological processes in liver and heart post MI. Finally, we validated our findings in two independent MI cohorts. Overall, our integrative analysis highlighted both common and specific biological responses to MI across a range of metabolically active tissues.

systems biology↗

bioRxiv2020

Multiplex recombinase polymerase amplification (RPA) assay developed using unique genomic regions and coupled with a lateral flow device for rapid on-site detection of genus Clavibacter and C. nebraskensis

Clavibacter is an agriculturally important bacterial genus comprising nine host-specific species/subspecies including C. nebraskensis (Cn), which causes Gosss wilt and blight of maize. A robust, simple, and field-deployable method is required to specifically detect Cn in infected plants and distinguish it from other Clavibacter species for quarantine purposes and timely disease management. A multiplex Recombinase Polymerase Amplification (RPA) coupled with a Lateral Flow Device (LFD) was developed for sensitive and rapid detection of Clavibacter and Cn directly from infected host. Unique and conserved genomic regions, the ABC transporter ATP-binding protein CDS/ABC-transporter permease and the MFS transporter gene, were used to design primers/probes for specific detection of genus Clavibacter and Cn, respectively. The assay was evaluated using 52 strains, representing all nine species/subspecies of Clavibacter, other closely related bacterial species, and naturally- and artificially-infected plant samples; no false positives or negatives were detected. The RPA reactions were also incubated in a closed hand at body temperature; results were again specific. The assay does not require DNA isolation and can be directly performed using host sap. The detection limit of 10 pg and 100 fg was determined for Clavibacter- and Cn-specific primers/probes, respectively. The detection limit for Cn-specific primer/probe set was decreased to 1,000 fg when 1 {micro}L of host sap was added into the RPA reaction containing 10-fold serially diluted genomic DNA; though no effect was observed on Clavibacter-specific primer/probe set. The assay is accurate and has applications at point-of-need diagnostics. This is the first multiplex RPA for any plant pathogen. IMPORTANCEClavibacter species are prevalent worldwide as have the potential to result in systemic infection. In the past, detection attempts have relied on both molecular- and immunological-based assays; however, current detection methods are time consuming and laborious. Field-deployable tests are desirable to identify potential samples infected with Clavibacter species. This study demonstrates that the field-deployable isothermal multi-target recombinase polymerase amplification can be performed for the simultaneous detection of the genus Clavibacter in general (all species), and C. nebraskensis, in particular, without specialized equipment. Additionally, the multiplex RPA coupled with a LFD may confer the benefits of faster detection and discrimination of Clavibacter species that affect critical regions susceptible to infection. This user-friendly format offers a flexible assay to complement both nucleic acid amplification and novel diagnosis methods without the need for DNA purification; this assay may serve as a point-of-reference for developing multiplex RPA assay for other plant pathogens.

microbiology↗

bioRxiv2019

Comparative genomics reveals signature regions used to develop a robust and sensitive multiplex TaqMan real-time qPCR assay to detect the genus Dickeya and Dickeya dianthicola

AimsDickeya species are high consequence plant pathogenic bacteria listed among the quarantine pathogens of the European Union; associated with potato disease outbreaks and subsequent economic losses worldwide. Early, accurate, and reliable detection of Dickeya spp. is needed to prevent establishment and further dissemination of this pathogen. Therefore, a multiplex TaqMan qPCR was developed for sensitive detection of Dickeya spp. and specifically, D. dianthicola. Methods and ResultsA signature genomic region for the genus Dickeya (mglA/mglC) and unique genomic region for D. dianthicola (alcohol dehydrogenase) were identified using a whole genome based comparative genomics approach. The developed multiplex TaqMan qPCR was validated using extensive inclusivity and exclusivity panels, and naturally/artificially infected samples to confirm broad range detection capability and specificity. Both sensitivity and spiked assays showed detection limit of 10 fg DNA. ConclusionThe developed multiplex assay is sensitive and reliable to detect Dickeya spp. and D. dianthicola with no false positives or false negatives. It was able to detect mixed infection from naturally and artificially infected plant materials. Significance and ImpactThe developed assay will serve as a practical tool for screening of propagative material, monitoring the presence and distribution, and quantification of target pathogens in a breeding program. The assay also has applications in routine diagnostics, biosecurity and microbial forensics.

plant biology↗

bioRxiv2019

Classification of clear cell renal cell carcinoma based on PKM alternative splicing

Clear cell renal cell carcinoma (ccRCC) accounts for 70-80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.

systems biology↗

bioRxiv2019

Proteolysis and neurogenesis modulated by LNR domain proteins explosion support male differentiation and sacrificial behaviour in the iteroparous crustacean Oithona nana.

Copepods are the most numerous animals and play an essential role in the marine trophic web and biogeochemical cycles. The genus Oithona is described as having the highest numerical density, as the most cosmopolite copepod and iteroparous. The Oithona male paradox obliges it to alternate feeding (immobile) and mating (mobile) phases. As the molecular basis of this trade-off is unknown, we investigated this sexual dimorphism at the molecular level by integrating genomic, transcriptomic and protein-protein interaction analyses.\n\nWhile a ZW sex-determination system was predicted in O. nana, a fifteen-year time-series in the Toulon Little Bay showed a biased sex ratio toward females (male / female ratio < 0.15{+/-}0.11) highlighting a higher mortality in male. Here, the transcriptomic analysis of the five different developmental stages showed enrichment of Lin12-Notch Repeat (LNR) domains-containing proteins coding genes (LDPGs) in male transcripts. The male also showed enrichment in transcripts involved in proteolysis, nervous system development, synapse assembly and functioning and also amino acid conversion to glutamate. Moreover, several male down-regulated genes were involved in the increase of food uptake and digestion. The formation of LDP complexes was detected by yeast two-hybrid, with interactions involving proteases, extracellular matrix proteins and neurogenesis related proteins.\n\nTogether, these results suggest that the O. nana male hypermotility is sustained by LDP-modulated proteolysis allowing the releases and conversions of amino acid into the excitatory neurotransmitter glutamate. This process could permit new axons and dendrites formation suggesting a sexual nervous system dimorphism. This could support the hypothesis of a sacrificial behaviour in males at the metabolic level.

molecular biology↗

bioRxiv2019

MOBN: an interactive database of multi-omics biological networks

It is essential to reveal the associations between different omics data for a comprehensive understanding of the altered biological process in human wellness and disease. To date, very few studies have focused on collecting and exhibiting multi-omics associations in a single database. Here, we present iNetModels, an interactive database and visualization platform of Multi-Omics Biological Networks (MOBNs). This platform describes the associations between the clinical chemistry, anthropometric parameters, plasma proteomics and metabolomics as well as metagenomics for oral and gut microbiome obtained from the same individuals. Moreover, iNetModels includes tissue- and cancer-specific Gene Co-expression Networks (GCNs) for exploring the connections between the specific genes. This platform allows the user to interactively explore a single feature's association with other omics data and customize its particular context (e.g. male/female specific). The users can also register their own data for sharing and visualization of the MOBNs and GCNs. Moreover, iNetModels allows users who do not have a bioinformatics background to facilitate human wellness and diseases research. iNetModels can be accessed freely at https://inetmodels.com without any limitation.

bioinformatics↗

bioRxiv2019

Discovery of functional alternatively spliced PKM transcripts in human cancers

The association of pyruvate kinase muscle type (PKM) with survival of cancer patients is controversial. Here, we focus on different transcripts of PKM and investigate the association between their mRNA expression and the clinical survival of the patients in 25 different cancers. We find that the transcript encoding PKM2, and three other functional transcripts are prognostic in multiple cancers. Our integrative analysis shows that the functions of these four transcripts are highly conservative in different cancers. Next, we validate the prognostic effect of these transcripts in an independent kidney renal clear-cell carcinoma (KIRC) cohort and identify a prognostic signature which could distinguish high- and low-risk KIRC patients. Finally, we reveal the functional role of alternatively spliced PKM transcripts in KIRC, and discover the protein products of different transcripts of PKM. Our analysis demonstrated that alternatively spliced transcripts of not only PKM but also other genes should be considered in cancer studies, since it may enable the discovery and targeting of the right protein product for development of the efficient treatment strategies.

systems biology↗

bioRxiv2019

Synergetic effect of non-complementary 5’ AT-rich sequences on the development of a multiplex TaqMan real-time PCR for specific and robust detection of Clavibacter michiganensis and C. michiganensis subsp. nebraskensis

Clavibacter is an agriculturally important genus comprising a single species, Clavibacter michiganensis, and multiple subspecies, including, C. michiganensis subsp. nebraskensis which causes Gosss wilt/blight of corn and accounts for high yield losses - listed among the five most significant diseases of corn in the United States of America. Our research objective was to develop a robust and rapid multiplex TaqMan real-time PCR (qPCR) to detect C. michiganensis in general and C. michiganensis subsp. nebraskensis with enhanced reliability and accuracy by adding non-complementary AT sequences to the 5 end of the forward and reverse primers. Comparative genomic analyses were performed to identify unique and conserved gene regions for primer and probe design. The unique genomic regions, ABC transporter ATP-binding protein CDS/ABC-transporter permease and MFS transporter were determined for specific detection of C. michiganensis and C. m. subsp. nebraskensis, respectively. The AT-rich sequences at the 5 position of the primers enhanced the reaction efficiency and sensitivity of rapid qPCR cycling; the reliability, accuracy and high efficiency of the developed assay was confirmed after testing with 59 strains from inclusivity and exclusivity panels - no false positives or false negatives were detected. The assays were also validated through naturally and artificially infected corn plant samples; all samples were detected for C. michiganensis and C. m. subsp. nebraskensis with 100% accuracy. The assay with 5 AT-rich sequences detected up to 10- and 100-fg of C. michiganensis and C. michiganensis subsp. nebraskensis genome targets, respectively. No adverse effect was observed when sensitivity assays were spiked with host genomic DNA. Addition of 5 AT rich sequences enhanced the qPCR reaction efficiency from 0.82 (M = -3.83) and 0.91 (M = -3.54) to 1.04 (with optimum slope value; M = -3.23) for both C. michiganensis and C. michiganensis subsp. nebraskensis, respectively; a increase of 10-fold sensitivity was also obtained with C. michiganensis primer set. The methodology proposed here can be used to optimize the reaction efficiency and to harmonize the diagnostic protocols which have prodigious applications in routine diagnostics, biosecurity and microbial forensics.

plant biology↗

bioRxiv2019

Spatiotemporal dissection of the cell cycle regulated human proteome

Cellular division is a fundamental source of cell-to-cell variability, and studies of transcript and protein abundances have revealed several hundred genes that are regulated by the cell cycle1-8. However, none of these studies provide single-cell resolution of protein expression, leaving an incomplete understanding of cell-to-cell heterogeneity and the roles of cycling transcripts and proteins. Here, we present the first comprehensive map of spatiotemporal heterogeneity of the human proteome by integrating proteomics at subcellular resolution, single-cell transcriptomics, and pseudotime measurements of individual cells within the cell cycle. We identify that 17% of the human proteome displays cell-to-cell variability, of which 26% is correlated to cell cycle progression, and we present the first evidence of cell cycle association for 235 proteins. Only 15% of proteomic cell cycle regulation is due to transcriptomic cycling, which points to other means of regulation such as post-translational modifications. For proteins regulated at the transcript level, we observe a 7.7 hour delay between peak expression of transcript and protein on average. This spatially resolved proteomic map of the cell cycle has been integrated into the Human Protein Atlas and serves as a valuable resource for accelerating molecular studies of the human cell cycle and cell proliferation.

cell biology↗