Publications by authors named "PETROVSKI S"

The prevalence of infections amongst intensive care unit (ICU) patients is inevitably high, and the ICU is considered the epicenter for the spread of multidrug-resistant bacteria. Multiple studies have focused on the microbial diversity largely inhabiting ICUs that continues to flourish despite treatment with various antibiotics, investigating the factors that influence the spread of these pathogens, with the aim of implementing sufficient monitoring and infection control methods. Despite joint efforts from healthcare providers and policymakers, ICUs remain a hub for healthcare-associated infections.

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The emergence of biobank-level datasets offers new opportunities to discover novel biomarkers and develop predictive algorithms for human disease. Here, we present an ensemble machine-learning framework (machine learning with phenotype associations, MILTON) utilizing a range of biomarkers to predict 3,213 diseases in the UK Biobank. Leveraging the UK Biobank's longitudinal health record data, MILTON predicts incident disease cases undiagnosed at time of recruitment, largely outperforming available polygenic risk scores.

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  • Telomeres are protective caps on chromosomes, and their length is related to aging and diseases, prompting a study on telomere length in over 462,000 UK Biobank participants.
  • Researchers created a new metric for measuring telomere length that improved understanding of its genetic control and identified 64 genetic variants and 30 genes linked to telomere length.
  • Notably, many of these genes are involved in clonal hematopoiesis, which is linked to certain cancers, indicating a complex relationship between rare genetic variants and telomere length.
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  • Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis, and the study investigates the role of soluble CD13 (sCD13) and its signaling through the bradykinin receptor B1 (B1R) in SSc pathogenesis.
  • Researchers found elevated levels of CD13, B1R, and MMP14 in skin from SSc patients, which contributed to fibrosis through signaling pathways activated by TGF-β and sCD13.
  • The study concludes that targeting the sCD13-B1R axis could represent a novel and effective therapeutic strategy for treating skin fibrosis in SSc.
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Gene misexpression is the aberrant transcription of a gene in a context where it is usually inactive. Despite its known pathological consequences in specific rare diseases, we have a limited understanding of its wider prevalence and mechanisms in humans. To address this, we analyzed gene misexpression in 4,568 whole-blood bulk RNA sequencing samples from INTERVAL study blood donors.

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The etiology of prostate cancer, the second most common cancer in men globally, has a strong heritable component. While rare coding germline variants in several genes have been identified as risk factors from candidate gene and linkage studies, the exome-wide spectrum of causal rare variants remains to be fully explored. To more comprehensively address their contribution, we analysed data from 37,184 prostate cancer cases and 331,329 male controls from five cohorts with germline exome/genome sequencing and one cohort with imputed array data from a population enriched in low-frequency deleterious variants.

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The ongoing expansion of human genomic datasets propels therapeutic target identification; however, extracting gene-disease associations from gene annotations remains challenging. Here, we introduce Mantis-ML 2.0, a framework integrating AstraZeneca's Biological Insights Knowledge Graph and numerous tabular datasets, to assess gene-disease probabilities throughout the phenome.

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The Burkholderia cepacia complex (Bcc) is a group of increasingly multi-drug resistant opportunistic bacteria. This resistance is driven through a combination of intrinsic factors and the carriage of a broad range of conjugative plasmids harbouring virulence determinants. Therefore, novel treatments are required to treat and prevent further spread of these virulence determinants.

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Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R.

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  • * The study focuses on 48 de novo missense variants in GRIN1, GRIN2A, and GRIN2B that affect the M3 transmembrane helix, identified in children with conditions like epilepsy and developmental delays.
  • * Most of these variants lead to a gain-of-function effect, promoting NMDAR channel activity, reinforcing the importance of the M3 region in receptor function, and providing insights into how certain drugs may affect these variant receptors.
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This review discusses critically how seasonal changes might affect the community composition and dynamics of activated sludge wastewater treatment plants (WWTP), and examines the factors thought more generally to control microbial community assembly, including the role of taxa-time relationships and stochastic and deterministic influences. The review also questions the differences in protocols used in these studies, which make any subsequent attempts at data comparisons problematic. These include bacterial DNA extraction and PCR methodologies, 16S rRNA sequencing and especially its depth, and subsequent statistical analyses of the data, which together often fail to reveal seasonal dynamic community shifts.

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African Americans have a significantly higher risk of developing chronic kidney disease, especially focal segmental glomerulosclerosis -, than European Americans. Two coding variants (G1 and G2) in the APOL1 gene play a major role in this disparity. While 13% of African Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

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In this study, we compared the genomes of three metal-resistant bacteria isolated from mercury-contaminated soil. We identified diverse and novel MGEs with evidence of multiple LGT events shaping their genomic structure and heavy metal resistance. Among the three metal-resistant strains, Sphingobium sp SA2 and Sphingopyxis sp SE2 were resistant to multiple metals including mercury, cadmium, copper, zinc and lead.

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Genomic medicine has been transformed by next-generation sequencing (NGS), inclusive of exome sequencing (ES) and genome sequencing (GS). Currently, ES is offered widely in clinical settings, with a less prevalent alternative model consisting of hybrid programs that incorporate research ES along with clinical patient workflows. We were among the earliest to implement a hybrid ES clinic, have provided diagnoses to 45% of probands, and have identified several novel candidate genes.

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  • The Mexico City Prospective Study is a large-scale research initiative involving over 150,000 adults from urban areas in Mexico City, aimed at understanding genetic diversity and ancestry.
  • The study reveals a mix of Indigenous American, European, and African ancestries among participants, highlighting significant genetic differences and a unique genetic landscape within the Indigenous Mexican population.
  • Researchers created a valuable reference panel for genetic research, improving the accuracy of studying genetic variants in populations with high Indigenous ancestry, and providing essential resources for future genetic studies in both Mexico and the US.
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  • The Pharma Proteomics Project is a large-scale research initiative analyzing blood protein profiles from over 54,000 UK Biobank participants to understand links between genetics and health.
  • The project identifies significant genetic associations with proteins, revealing many novel interactions and highlighting ancestry-specific variations, along with insights into disease mechanisms and potential drug targets.
  • By making their findings publicly accessible, the consortium aims to advance research in biomarker development and therapeutic strategies, enhancing our understanding of how genetic factors influence health outcomes.
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Integrating human genomics and proteomics can help elucidate disease mechanisms, identify clinical biomarkers and discover drug targets. Because previous proteogenomic studies have focused on common variation via genome-wide association studies, the contribution of rare variants to the plasma proteome remains largely unknown. Here we identify associations between rare protein-coding variants and 2,923 plasma protein abundances measured in 49,736 UK Biobank individuals.

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, a plant pathogen, is primarily transmitted through contaminated seeds and insect vectors, with the corn flea beetle () being the primary carrier. is a bacterium belonging to the order and can lead to crop diseases that have a significant economic impact worldwide. Due to its high potential for spread, is classified as a quarantine organism in numerous countries.

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Objectives: Providencia is a genus of gram-negative bacteria within the order Enterobacterales, closely related to Proteus and Morganella. While ubiquitous in the environment, some species of Providencia, such as P. rettgeri and P.

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Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic.

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Objective: Hospitals serve as hotspots of antibiotic resistance. Despite several studies exploring antibiotic resistance in hospitals, none have explored the resistance profile of soil bacteria from a hospital precinct. This study examined and compared the antibiogram of the soil isolates from a hospital and its affiliated university precinct, to determine if antibiotic resistant bacteria were present closer to the hospital.

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Black Americans have a significantly higher risk of developing chronic kidney disease (CKD), especially focal segmental glomerulosclerosis (FSGS), than European Americans. Two coding variants (G1 and G2) in the gene play a major role in this disparity. While 13% of Black Americans carry the high-risk recessive genotypes, only a fraction of these individuals develops FSGS or kidney failure, indicating the involvement of additional disease modifiers.

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