ORCID Profile
0000-0002-9458-3061
Current Organisation
Peter MacCallum Cancer Centre
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Publisher: F1000 Research Ltd
Date: 08-06-2016
DOI: 10.12688/F1000RESEARCH.8839.1
Abstract: Methylation in the human genome is known to be associated with development and disease. The Illumina Infinium methylation arrays are by far the most common way to interrogate methylation across the human genome. This paper provides a Bioconductor workflow using multiple packages for the analysis of methylation array data. Specifically, we demonstrate the steps involved in a typical differential methylation analysis pipeline including: quality control, filtering, normalization, data exploration and statistical testing for probe-wise differential methylation. We further outline other analyses such as differential methylation of regions, differential variability analysis, estimating cell type composition and gene ontology testing. Finally, we provide some ex les of how to visualise methylation array data.
Publisher: F1000 Research Ltd
Date: 26-07-2016
DOI: 10.12688/F1000RESEARCH.8839.2
Abstract: Methylation in the human genome is known to be associated with development and disease. The Illumina Infinium methylation arrays are by far the most common way to interrogate methylation across the human genome. This paper provides a Bioconductor workflow using multiple packages for the analysis of methylation array data. Specifically, we demonstrate the steps involved in a typical differential methylation analysis pipeline including: quality control, filtering, normalization, data exploration and statistical testing for probe-wise differential methylation. We further outline other analyses such as differential methylation of regions, differential variability analysis, estimating cell type composition and gene ontology testing. Finally, we provide some ex les of how to visualise methylation array data.
Publisher: Springer Science and Business Media LLC
Date: 03-10-2013
DOI: 10.1038/NCOMMS3537
Publisher: F1000 Research Ltd
Date: 05-04-2017
DOI: 10.12688/F1000RESEARCH.8839.3
Abstract: Methylation in the human genome is known to be associated with development and disease. The Illumina Infinium methylation arrays are by far the most common way to interrogate methylation across the human genome. This paper provides a Bioconductor workflow using multiple packages for the analysis of methylation array data. Specifically, we demonstrate the steps involved in a typical differential methylation analysis pipeline including: quality control, filtering, normalization, data exploration and statistical testing for probe-wise differential methylation. We further outline other analyses such as differential methylation of regions, differential variability analysis, estimating cell type composition and gene ontology testing. Finally, we provide some ex les of how to visualise methylation array data.
Publisher: American Society for Clinical Investigation
Date: 06-09-2018
Publisher: Elsevier BV
Date: 05-2019
Publisher: Frontiers Media SA
Date: 25-04-2018
Publisher: Cold Spring Harbor Laboratory
Date: 17-06-2022
DOI: 10.1101/2022.06.17.496207
Abstract: Inflammation is a key driver of cystic fibrosis (CF) lung disease, not addressed by current standard care. Improved understanding of the mechanisms leading to aberrant inflammation may assist the development of effective anti-inflammatory therapy. Single-cell RNA sequencing (scRNA-seq) allows profiling of cell composition and function at previously unprecedented resolution. Herein, we seek to use multimodal single-cell analysis to comprehensively define immune cell phenotypes, proportions and functional characteristics in preschool children with CF. We analyzed 42,658 cells from bronchoalveolar lavage of 11 preschool children with CF and a healthy control using scRNA-seq and parallel assessment of 154 cell surface proteins. Validation of cell types identified by scRNA-seq was achieved by assessment of s les by spectral flow cytometry. Analysis of transcriptome expression and cell surface protein expression, combined with functional pathway analysis, revealed 41 immune and epithelial cell populations in BAL. Spectral flow cytometry analysis of over 256,000 cells from a subset of the same patients revealed high correlation in major cell type proportions across the two technologies. Macrophages consisted of 13 functionally distinct sub populations, including previously undescribed populations enriched for markers of vesicle production and regulatory/repair functions. Other novel cell populations included CD4 T cells expressing inflammatory IFNα/β and NFκB signalling genes. Our work provides a comprehensive cellular analysis of the pediatric lower airway in preschool children with CF, reveals novel cell types and provides a reference for investigation of inflammation in early life CF.
Publisher: Oxford University Press (OUP)
Date: 18-03-2015
Publisher: Oxford University Press (OUP)
Date: 07-2013
Publisher: American Society for Cell Biology (ASCB)
Date: 08-2018
Abstract: Mouse models have shown that a disintegrin A metalloprotease 12 (ADAM12) is implicated during adipogenesis the molecular pathways are not well understood. Stealth RNA interference was used to knock down ADAM12 in 3T3-L1 cells. Using gene profiling and metabolic enzymatic markers, we have identified signaling pathways ADAM12 impacts upon during proliferation, differentiation, and maturation of adipocytes. ADAM12 reduced cell numbers in proliferating preadipocytes, delayed differentiation of preadipocytes to adipocytes, and increased lipid accumulation in mature adipocytes. The pathway most affected by ADAM12 knockdown was regulation of insulin-like growth factor (IGF) activity by insulin-like growth factor binding proteins (IGFBPs) ADAM12 is known to cleave IGFBP3 and IGFBP5. The IGF/mTOR signaling pathway was down-regulated, supporting a role for ADAM12 in the IGFBP/IGF/mTOR-growth pathway. PPARγ signaling was also down-regulated by ADAM12 knockdown. Gene ontology (GO) analysis revealed that the extracellular matrix was the cellular compartment most impacted. Filtering for matrisome genes, connective tissue growth factor ( Ctgf) was up-regulated. CTGF and IGBP3 can interact with PPARγ to hinder its regulation. Increased expression of these molecules could have influenced PPARγ signaling reducing differentiation and an imbalance of lipids. We believe ADAM12 regulates cell proliferation of preadipocytes through IGFBP/IGF/mTOR signaling and delays differentiation through altered PPAR signaling to cause an imbalance of lipids within mature adipocytes.
Publisher: American Society of Hematology
Date: 31-07-2014
DOI: 10.1182/BLOOD-2013-12-544106
Abstract: Ezh2 represses Ifng, Gata3, and Il10 loci in naïve CD4+T cells, and its deficiency leads to Th1 skewing and IL-10 overproduction in Th2 cells. Ezh2 deficiency activates multiple death pathways in differentiated effector Th cells.
Publisher: Oxford University Press (OUP)
Date: 22-11-2011
Abstract: Milk sialoglycoconjugates can protect the gastrointestinal tract of the suckling neonate by competitively binding to invading pathogens and promoting growth of beneficial flora, and their potential role in postnatal brain development is of particular interest in human infant nutrition. Although the concentration and the distribution of sialoglycoconjugates have been extensively studied in the milk of various species, the investigation of sialyltransferase gene expression in the mammary gland, in the context of lactation, has been limited. The sialyltransferase enzyme ST6Gal I transfers sialic acid from CMP-sialic acid to type 2 (Galβ1,4GlcNAc) free disaccharides or the termini of N- or O-linked oligosaccharides using an α2,6-linkage. Expression of the ST6Gal I gene is primarily regulated at the level of transcription through the use of several cell and development-specific promoters, producing transcripts with ergent 5' untranslated regions (UTR). In the mouse mammary gland, the novel 5'UTR exon (L) appears to be associated with a drastic increase in ST6Gal I gene expression during lactation. We find that rats also possess an exon (L), suggesting conservation of this regulatory mechanism in rodents. In contrast, an exon (L)-containing transcript was not detected in the lactating bovine or human mammary gland. We also observed a trend of increasing ST6Gal I gene expression in the bovine mammary gland, culminating in involution. This is in contrast to species such as mice where the greatest change in ST6Gal I gene expression occurs between pregnancy and lactation, suggesting different roles in rodents vs. other mammals for α2,6-sialylated oligosaccharides present in milk.
Publisher: Cold Spring Harbor Laboratory
Date: 25-08-2020
DOI: 10.1101/2020.08.24.265702
Abstract: DNA methylation is one of the most commonly studied epigenetic marks, due to its role in disease and development. Illumina methylation arrays have been extensively used to measure methylation across the human genome. Methylation array analysis has primarily focused on preprocessing, normalisation and identification of differentially methylated CpGs and regions. GOmeth and GOregion are new methods for performing unbiased gene set testing following differential methylation analysis. Benchmarking analyses demonstrate GOmeth outperforms other approaches and GOregion is the first method for gene set testing of differentially methylated regions. Both methods are publicly available in the missMethyl Bioconductor R package.
Publisher: Cold Spring Harbor Laboratory
Date: 21-12-2022
DOI: 10.1101/2022.12.20.521313
Abstract: S le multiplexing is often used to reduce cost and limit batch effects in single-cell RNA sequencing (scRNA-seq) experiments. A commonly used multiplexing technique involves tagging cells prior to pooling with a hashtag oligo (HTO) that can be sequenced along with the cells’ RNA to determine their s le of origin. Several tools have been developed to demultiplex HTO sequencing data and assign cells to s les. In this study, we critically assess the performance of seven HTO demultiplexing tools: hashedDrops, HTODemux, GMM-Demux, demuxmix, deMULTIplex, BFF and HashSolo . The comparison uses data sets where each s le has also been demultiplexed using genetic variants from the RNA, enabling comparison of HTO demultiplexing techniques against complementary data from the genetic “ground truth”. We find that all methods perform similarly where HTO labelling is of high quality, but methods that assume a bimodal counts distribution perform poorly on lower quality data. We also suggest heuristic approaches for assessing the quality of HTO counts in a scRNA-seq experiment.
Publisher: Oxford University Press (OUP)
Date: 30-09-2016
DOI: 10.1093/BIOINFORMATICS/BTV560
Abstract: Summary: DNA methylation is one of the most commonly studied epigenetic modifications due to its role in both disease and development. The Illumina HumanMethylation450 BeadChip is a cost-effective way to profile & 000 CpGs across the human genome, making it a popular platform for profiling DNA methylation. Here we introduce missMethyl, an R package with a suite of tools for performing normalization, removal of unwanted variation in differential methylation analysis, differential variability testing and gene set analysis for the 450K array. Availability and implementation: missMethyl is an R package available from the Bioconductor project at www.bioconductor.org. Contact: alicia.oshlack@mcri.edu.au Supplementary information: Supplementary data are available at Bioinformatics online.
Publisher: American Thoracic Society
Date: 05-2019
DOI: 10.1164/AJRCCM-CONFERENCE.2019.199.1_MEETINGABSTRACTS.A7333
Publisher: Oxford University Press (OUP)
Date: 18-05-2015
DOI: 10.1093/NAR/GKV526
Publisher: Elsevier BV
Date: 10-2022
Publisher: American Society of Hematology
Date: 17-10-2013
DOI: 10.1182/BLOOD-2013-02-481788
Abstract: Human naive CD4+ T cells and resting nTreg are differentially methylated at 127 regions in their genomic DNA. Forkhead-binding motifs are present in promoter-associated differentially methylated regions, inferring broader epigenetic control of Treg.
Publisher: Springer Science and Business Media LLC
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 12-04-2012
DOI: 10.1038/GENE.2012.7
Abstract: The aim of this study was to investigate the dynamics and relationship between DNA methylation and gene expression during early T-cell development. Mononuclear cells were collected at birth and at 12 months from 60 infants and were either activated with anti-CD3 for 24 h or cultured in media alone, and the CD4+ T-cell subset purified. DNA and RNA were co-harvested and DNA methylation was measured in 450 000 CpG sites in parallel with expression measurements taken from 25 000 genes. In unstimulated cells, we found that a subset of 1188 differentially methylated loci were associated with a change in expression in 599 genes (adjusted P value 0.1). These genes were enriched in reprogramming regions of the genome known to control pluripotency. In contrast, over 630 genes were induced following low-level T-cell activation, but this was not associated with any significant change in DNA methylation. We conclude that DNA methylation is dynamic during early T-cell development, and has a role in the consolidation of T-cell-specific gene expression. During the early phase of clonal expansion, DNA methylation is stable and therefore appears to be of limited importance in short-term T-cell responsiveness.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Springer Science and Business Media LLC
Date: 06-2014
Publisher: Springer Science and Business Media LLC
Date: 17-10-2016
DOI: 10.1038/NBT.3702
Abstract: The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.BBAGRM.2017.01.014
Abstract: During development, the α- and β-globin genes exhibit a highly conserved pattern of expression, giving rise to several developmental stage-specific hemoglobin variants. Networks of regulatory proteins interact with epigenetic complexes to regulate DNA accessibility and histone modifications, thereby determining appropriate patterns of globin gene expression. In this review, we focus on recent advances in the understanding of the molecular mechanisms that underpin globin gene expression, focusing on multi-subunit regulatory complexes that bind to specific regions of DNA to orchestrate globin gene transcription throughout development.
No related grants have been discovered for Jovana Maksimovic.