14 results on '"Khabirova E"'
Search Results
2. Resources to develop the research publication competencies of Russian researchers
- Author
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Popova, N. G., primary and Khabirova, E. I., additional
- Published
- 2023
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3. Сontаminаtion of soil with pаthogens of helminth-protozoаlinvаsions in Аstrаkhаn Region for 2016–2020
- Author
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Nikeshina, T. V., primary, Аrаkelyаn, R. S., additional, Shendo, G. L., additional, Boldyrevа, A. I., additional, Sаlikhov, N. Z., additional, Khabirova, E. R., additional, Bolurova, A. M., additional, Kharkibenov, B. N., additional, Davletkazieva, A. Kh., additional, and Kulzhanova, M. S., additional
- Published
- 2022
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4. An integrated single-cell analysis of human adrenal cortex development.
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Del Valle I, Young MD, Kildisiute G, Ogunbiyi OK, Buonocore F, Simcock IC, Khabirova E, Crespo B, Moreno N, Brooks T, Niola P, Swarbrick K, Suntharalingham JP, McGlacken-Byrne SM, Arthurs OJ, Behjati S, and Achermann JC
- Subjects
- Infant, Newborn, Humans, Hydrocortisone metabolism, Adrenal Glands metabolism, Steroids, Homeodomain Proteins metabolism, Aldosterone metabolism, Adrenal Cortex
- Abstract
The adrenal glands synthesize and release essential steroid hormones such as cortisol and aldosterone, but many aspects of human adrenal gland development are not well understood. Here, we combined single-cell and bulk RNA sequencing, spatial transcriptomics, IHC, and micro-focus computed tomography to investigate key aspects of adrenal development in the first 20 weeks of gestation. We demonstrate rapid adrenal growth and vascularization, with more cell division in the outer definitive zone (DZ). Steroidogenic pathways favored androgen synthesis in the central fetal zone, but DZ capacity to synthesize cortisol and aldosterone developed with time. Core transcriptional regulators were identified, with localized expression of HOPX (also known as Hop homeobox/homeobox-only protein) in the DZ. Potential ligand-receptor interactions between mesenchyme and adrenal cortex were seen (e.g., RSPO3/LGR4). Growth-promoting imprinted genes were enriched in the developing cortex (e.g., IGF2, PEG3). These findings reveal aspects of human adrenal development and have clinical implications for understanding primary adrenal insufficiency and related postnatal adrenal disorders, such as adrenal tumor development, steroid disorders, and neonatal stress.
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- 2023
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5. Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia.
- Author
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Anderson ND, Birch J, Accogli T, Criado I, Khabirova E, Parks C, Wood Y, Young MD, Porter T, Richardson R, Albon SJ, Popova B, Lopes A, Wynn R, Hough R, Gohil SH, Pule M, Amrolia PJ, Behjati S, and Ghorashian S
- Subjects
- Humans, Antigens, CD19 genetics, Immunotherapy, Adoptive, Receptors, Antigen, T-Cell, Remission Induction, T-Lymphocytes, Leukemia, Lymphocytic, Chronic, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy
- Abstract
In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists., (© 2023. The Author(s).)
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- 2023
- Full Text
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6. Babesia duncani multi-omics identifies virulence factors and drug targets.
- Author
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Singh P, Lonardi S, Liang Q, Vydyam P, Khabirova E, Fang T, Gihaz S, Thekkiniath J, Munshi M, Abel S, Ciampossin L, Batugedara G, Gupta M, Lu XM, Lenz T, Chakravarty S, Cornillot E, Hu Y, Ma W, Gonzalez LM, Sánchez S, Estrada K, Sánchez-Flores A, Montero E, Harb OS, Le Roch KG, and Mamoun CB
- Subjects
- Animals, Humans, Mice, Multiomics, Erythrocytes parasitology, Babesia genetics, Babesiosis drug therapy, Ticks
- Abstract
Babesiosis is a malaria-like disease in humans and animals that is caused by Babesia species, which are tick-transmitted apicomplexan pathogens. Babesia duncani causes severe to lethal infection in humans, but despite the risk that this parasite poses as an emerging pathogen, little is known about its biology, metabolic requirements or pathogenesis. Unlike other apicomplexan parasites that infect red blood cells, B. duncani can be continuously cultured in vitro in human erythrocytes and can infect mice resulting in fulminant babesiosis and death. We report comprehensive, detailed molecular, genomic, transcriptomic and epigenetic analyses to gain insights into the biology of B. duncani. We completed the assembly, 3D structure and annotation of its nuclear genome, and analysed its transcriptomic and epigenetics profiles during its asexual life cycle stages in human erythrocytes. We used RNA-seq data to produce an atlas of parasite metabolism during its intraerythrocytic life cycle. Characterization of the B. duncani genome, epigenome and transcriptome identified classes of candidate virulence factors, antigens for diagnosis of active infection and several attractive drug targets. Furthermore, metabolic reconstitutions from genome annotation and in vitro efficacy studies identified antifolates, pyrimethamine and WR-99210 as potent inhibitors of B. duncani to establish a pipeline of small molecules that could be developed as effective therapies for the treatment of human babesiosis., (© 2023. The Author(s).)
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- 2023
- Full Text
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7. Precise identification of cancer cells from allelic imbalances in single cell transcriptomes.
- Author
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Trinh MK, Pacyna CN, Kildisiute G, Thevanesan C, Piapi A, Ambridge K, Anderson ND, Khabirova E, Prigmore E, Straathof K, Behjati S, and Young MD
- Subjects
- Allelic Imbalance genetics, Genotype, Humans, Polymorphism, Single Nucleotide, RNA, Messenger genetics, Neoplasms diagnosis, Neoplasms genetics, Transcriptome
- Abstract
A fundamental step of tumour single cell mRNA analysis is separating cancer and non-cancer cells. We show that the common approach to separation, using shifts in average expression, can lead to erroneous biological conclusions. By contrast, allelic imbalances representing copy number changes directly detect the cancer genotype and accurately separate cancer from non-cancer cells. Our findings provide a definitive approach to identifying cancer cells from single cell mRNA sequencing data., (© 2022. The Author(s).)
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- 2022
- Full Text
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8. Single-cell transcriptomics reveals a distinct developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia.
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Khabirova E, Jardine L, Coorens THH, Webb S, Treger TD, Engelbert J, Porter T, Prigmore E, Collord G, Piapi A, Teichmann SA, Inglott S, Williams O, Heidenreich O, Young MD, Straathof K, Bomken S, Bartram J, Haniffa M, and Behjati S
- Subjects
- Bone Marrow metabolism, Child, Gene Rearrangement genetics, Humans, Infant, Mutation genetics, Myeloid-Lymphoid Leukemia Protein genetics, Precursor Cell Lymphoblastic Leukemia-Lymphoma genetics, Transcriptome genetics
- Abstract
KMT2A-rearranged infant ALL is an aggressive childhood leukemia with poor prognosis. Here, we investigated the developmental state of KMT2A-rearranged infant B-cell acute lymphoblastic leukemia (B-ALL) using bulk messenger RNA (mRNA) meta-analysis and examination of single lymphoblast transcriptomes against a developing bone marrow reference. KMT2A-rearranged infant B-ALL was uniquely dominated by an early lymphocyte precursor (ELP) state, whereas less adverse NUTM1-rearranged infant ALL demonstrated signals of later developing B cells, in line with most other childhood B-ALLs. We compared infant lymphoblasts with ELP cells and revealed that the cancer harbored hybrid myeloid-lymphoid features, including nonphysiological antigen combinations potentially targetable to achieve cancer specificity. We validated surface coexpression of exemplar combinations by flow cytometry. Through analysis of shared mutations in separate leukemias from a child with infant KMT2A-rearranged B-ALL relapsing as AML, we established that KMT2A rearrangement occurred in very early development, before hematopoietic specification, emphasizing that cell of origin cannot be inferred from the transcriptional state., (© 2022. The Author(s).)
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- 2022
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9. Single cell derived mRNA signals across human kidney tumors.
- Author
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Young MD, Mitchell TJ, Custers L, Margaritis T, Morales-Rodriguez F, Kwakwa K, Khabirova E, Kildisiute G, Oliver TRW, de Krijger RR, van den Heuvel-Eibrink MM, Comitani F, Piapi A, Bugallo-Blanco E, Thevanesan C, Burke C, Prigmore E, Ambridge K, Roberts K, Braga FAV, Coorens THH, Del Valle I, Wilbrey-Clark A, Mamanova L, Stewart GD, Gnanapragasam VJ, Rampling D, Sebire N, Coleman N, Hook L, Warren A, Haniffa M, Kool M, Pfister SM, Achermann JC, He X, Barker RA, Shlien A, Bayraktar OA, Teichmann SA, Holstege FC, Meyer KB, Drost J, Straathof K, and Behjati S
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- Adult, Algorithms, Child, Fetus metabolism, Gene Expression Regulation, Developmental, Humans, Kidney embryology, Kidney Neoplasms embryology, Kidney Neoplasms metabolism, Models, Genetic, Signal Transduction genetics, Kidney metabolism, Kidney Neoplasms genetics, RNA, Messenger genetics, RNA-Seq methods, Single-Cell Analysis methods, Transcriptome
- Abstract
Tumor cells may share some patterns of gene expression with their cell of origin, providing clues into the differentiation state and origin of cancer. Here, we study the differentiation state and cellular origin of 1300 childhood and adult kidney tumors. Using single cell mRNA reference maps of normal tissues, we quantify reference "cellular signals" in each tumor. Quantifying global differentiation, we find that childhood tumors exhibit fetal cellular signals, replacing the presumption of "fetalness" with a quantitative measure of immaturity. By contrast, in adult cancers our assessment refutes the suggestion of dedifferentiation towards a fetal state in most cases. We find an intimate connection between developmental mesenchymal populations and childhood renal tumors. We demonstrate the diagnostic potential of our approach with a case study of a cryptic renal tumor. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
- Published
- 2021
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10. Somatic mutations and single-cell transcriptomes reveal the root of malignant rhabdoid tumours.
- Author
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Custers L, Khabirova E, Coorens THH, Oliver TRW, Calandrini C, Young MD, Vieira Braga FA, Ellis P, Mamanova L, Segers H, Maat A, Kool M, Hoving EW, van den Heuvel-Eibrink MM, Nicholson J, Straathof K, Hook L, de Krijger RR, Trayers C, Allinson K, Behjati S, and Drost J
- Subjects
- Cell Differentiation genetics, DNA Methylation, Drug Screening Assays, Antitumor, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Histone Deacetylase Inhibitors pharmacology, Humans, Neural Crest pathology, Phylogeny, Rhabdoid Tumor drug therapy, SMARCB1 Protein genetics, Single-Cell Analysis, TOR Serine-Threonine Kinases antagonists & inhibitors, Tissue Culture Techniques methods, Mutation, Rhabdoid Tumor genetics, Rhabdoid Tumor pathology
- Abstract
Malignant rhabdoid tumour (MRT) is an often lethal childhood cancer that, like many paediatric tumours, is thought to arise from aberrant fetal development. The embryonic root and differentiation pathways underpinning MRT are not firmly established. Here, we study the origin of MRT by combining phylogenetic analyses and single-cell mRNA studies in patient-derived organoids. Comparison of somatic mutations shared between cancer and surrounding normal tissues places MRT in a lineage with neural crest-derived Schwann cells. Single-cell mRNA readouts of MRT differentiation, which we examine by reverting the genetic driver mutation underpinning MRT, SMARCB1 loss, suggest that cells are blocked en route to differentiating into mesenchyme. Quantitative transcriptional predictions indicate that combined HDAC and mTOR inhibition mimic MRT differentiation, which we confirm experimentally. Our study defines the developmental block of MRT and reveals potential differentiation therapies.
- Published
- 2021
- Full Text
- View/download PDF
11. Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell.
- Author
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Kildisiute G, Kholosy WM, Young MD, Roberts K, Elmentaite R, van Hooff SR, Pacyna CN, Khabirova E, Piapi A, Thevanesan C, Bugallo-Blanco E, Burke C, Mamanova L, Keller KM, Langenberg-Ververgaert KPS, Lijnzaad P, Margaritis T, Holstege FCP, Tas ML, Wijnen MHWA, van Noesel MM, Del Valle I, Barone G, van der Linden R, Duncan C, Anderson J, Achermann JC, Haniffa M, Teichmann SA, Rampling D, Sebire NJ, He X, de Krijger RR, Barker RA, Meyer KB, Bayraktar O, Straathof K, Molenaar JJ, and Behjati S
- Subjects
- Child, Humans, Neural Crest metabolism, RNA, Messenger genetics, Transcriptome, Neural Stem Cells metabolism, Neuroblastoma genetics, Neuroblastoma metabolism, Neuroblastoma pathology
- Abstract
Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer ( n = 19,723) with normal fetal adrenal single-cell transcriptomes ( n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)
- Published
- 2021
- Full Text
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12. Big data augmentated business trend identification: the case of mobile commerce.
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Saritas O, Bakhtin P, Kuzminov I, and Khabirova E
- Abstract
Identifying and monitoring business and technological trends are crucial for innovation and competitiveness of businesses. Exponential growth of data across the world is invaluable for identifying emerging and evolving trends. On the other hand, the vast amount of data leads to information overload and can no longer be adequately processed without the use of automated methods of extraction, processing, and generation of knowledge. There is a growing need for information systems that would monitor and analyse data from heterogeneous and unstructured sources in order to enable timely and evidence-based decision-making. Recent advancements in computing and big data provide enormous opportunities for gathering evidence on future developments and emerging opportunities. The present study demonstrates the use of text-mining and semantic analysis of large amount of documents for investigating in business trends in mobile commerce (m-commerce). Particularly with the on-going COVID-19 pandemic and resultant social isolation, m-commerce has become a large technology and business domain with ever growing market potentials. Thus, our study begins with a review of global challenges, opportunities and trends in the development of m-commerce in the world. Next, the study identifies critical technologies and instruments for the full utilization of the potentials in the sector by using the intelligent big data analytics system based on in-depth natural language processing utilizing text-mining, machine learning, science bibliometry and technology analysis. The results generated by the system can be used to produce a comprehensive and objective web of interconnected technologies, trends, drivers and barriers to give an overview of the whole landscape of m-commerce in one business intelligence (BI) data mart diagram., (© Akadémiai Kiadó, Budapest, Hungary 2021.)
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- 2021
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13. Flyglow: Single-fly observations of simultaneous molecular and behavioural circadian oscillations in controls and an Alzheimer's model.
- Author
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Khabirova E, Chen KF, O'Neill JS, and Crowther DC
- Abstract
Circadian rhythms are essential for health and are frequently disturbed in disease. A full understanding of the causal relationships between behavioural and molecular circadian rhythms requires simultaneous longitudinal observations over time in individual organisms. Current experimental paradigms require the measurement of each rhythm separately across distinct populations of experimental organisms, rendering the comparability of the resulting datasets uncertain. We therefore developed FLYGLOW, an assay using clock gene controlled luciferase expression detected by exquisitely sensitive EM-CCD imaging, to enable simultaneous quantification of parameters including locomotor, sleep consolidation and molecular rhythms in single flies over days/weeks. FLYGLOW combines all the strengths of existing techniques, and also allows powerful multiparametric paired statistics. We found the age-related transition from rhythmicity to arrhythmicity for each parameter occurs unpredictably, with some flies showing loss of one or more rhythms during middle-age. Using single-fly correlation analysis of rhythm robustness and period we demonstrated the independence of the peripheral clock from circadian behaviours in wild type flies as well as in an Alzheimer's model. FLYGLOW is a useful tool for investigating the deterioration of behavioural and molecular rhythms in ageing and neurodegeneration. This approach may be applied more broadly within behavioural neurogenetics research.
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- 2016
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14. The TRiC/CCT chaperone is implicated in Alzheimer's disease based on patient GWAS and an RNAi screen in Aβ-expressing Caenorhabditis elegans.
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Khabirova E, Moloney A, Marciniak SJ, Williams J, Lomas DA, Oliver SG, Favrin G, Sattelle DB, and Crowther DC
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- Animals, Humans, Phenotype, Alzheimer Disease genetics, Amyloid beta-Peptides genetics, Caenorhabditis elegans genetics, Genome-Wide Association Study, Molecular Chaperones physiology, RNA Interference
- Abstract
The human Aβ peptide causes progressive paralysis when expressed in the muscles of the nematode worm, C. elegans. We have exploited this model of Aβ toxicity by carrying out an RNAi screen to identify genes whose reduced expression modifies the severity of this locomotor phenotype. Our initial finding was that none of the human orthologues of these worm genes is identical with the genome-wide significant GWAS genes reported to date (the "white zone"); moreover there was no identity between worm screen hits and the longer list of GWAS genes which included those with borderline levels of significance (the "grey zone"). This indicates that Aβ toxicity should not be considered as equivalent to sporadic AD. To increase the sensitivity of our analysis, we then considered the physical interactors (+1 interactome) of the products of the genes in both the worm and the white+grey zone lists. When we consider these worm and GWAS gene lists we find that 4 of the 60 worm genes have a +1 interactome overlap that is larger than expected by chance. Two of these genes form a chaperonin complex, the third is closely associated with this complex and the fourth gene codes for actin, the major substrate of the same chaperonin.
- Published
- 2014
- Full Text
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