Papers by Vijayachitra Modhukur
MBMethPred: Medulloblastoma Subgroups Prediction
Additional file 1 of Chromatin modifier developmental pluripotency associated factor 4 (DPPA4) is a candidate gene for alcohol-induced developmental disorders
Figshare, 2023
1133 ECLAI: personalized clinical management of endometrial cancer using liquid biopsy, genomics and artificial intelligence
bioRxiv (Cold Spring Harbor Laboratory), Feb 29, 2024
Current therapeutics of endometriosis are limited to hormonal action on endometriotic lesions to ... more Current therapeutics of endometriosis are limited to hormonal action on endometriotic lesions to disrupt their growth. Based on the recent findings of the high utilization of glycolysis over oxidative metabolism (Warburg-like effect) in endometriotic lesions, a new strategy of nonhormonal management by addressing cellular metabolism has been proposed. However, it remains unclear which cell types are metabolically altered and contribute to endometriotic lesion growth for targeting them with metabolic drugs. Using single-cell RNA-sequencing, we investigated the activity of twelve metabolic pathways and genes involved in steroidogenesis in paired samples of eutopic endometrium (EuE) and peritoneal lesions (ectopic endometrium, EcE) from women with confirmed endometriosis. We detected nine major cell clusters in both EuE and EcE. The metabolic pathways were differentially regulated in perivascular, stromal and to a lesser extent in endothelial cell clusters, with the highest changes in AMP-activated protein kinase signaling, Hypoxia-Inducible Factor-1 signaling, glutathione metabolism, oxidative phosphorylation, and glycolysis/gluconeogenesis. We identified a transcriptomic co-activation of glycolysis and oxidative metabolism in perivascular and stromal cells of EcE compared with EuE, suggesting that metabolic reprogramming may play a critical role in maintaining cell growth and survival of endometriotic lesions. Additionally, progesterone receptor was significantly downregulated in perivascular and endothelial cells of EcE. The expression of estrogen receptor 1 was significantly reduced in perivascular, stromal and endothelial cells of EcE. In parallel, perivascular cells exhibited a high expression of estrogen receptor 2 and HSD17B8 gene that encodes for protein converting estrone (E1) to estradiol (E2), while in endothelial cells HSD17B2 gene coding for enzyme converting E2 to E1 was downregulated. Overall, our results identified different expression patterns of energy metabolic pathways and steroidogenesis-related genes in perivascular, stromal, and endothelial cells in EcE compared with EuE. Perivascular cells, known to contribute to the restoration of endometrial stroma and angiogenesis, can be a potential target for non-hormonal treatment of endometriosis. .
Scientific reports, Feb 21, 2024
The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and... more The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and most glioblastoma patients die from the disease recurrence. Thus, systematic studies in simplified model systems are required to pinpoint the choice of targets for further exploration in clinical settings. Here, we report screening of 5 compounds targeting epigenetic writers or erasers and 6 compounds targeting cell cycle-regulating protein kinases against 3 glioblastoma cell lines following incubation under normoxic or hypoxic conditions. The viability/proliferation assay indicated that PRMT5 inhibitor onametostat was endowed with high potency under both normoxic and hypoxic conditions in cell lines that are strongly MGMT-positive (T98-G), weakly MGMT-positive (U-251 MG), or MGMT-negative (U-87 MG). In U-251 MG and U-87 MG cells, onametostat also affected the spheroid formation at concentrations lower than the currently used chemotherapeutic drug lomustine. In T98-G cell line, treatment with onametostat led to dramatic changes in the transcriptome profile by inducing the cell cycle arrest, suppressing RNA splicing, and down-regulating several major glioblastoma cell survival pathways. Further validation by immunostaining in three cell lines confirmed that onametostat affects cell cycle and causes reduction in nucleolar protein levels. In this way, inhibition of epigenetic targets might represent a viable strategy for glioblastoma treatment even in the case of decreased chemoand radiation sensitivity, although further studies in clinically more relevant models are required. Glioblastoma (GB) is a highly aggressive and lethal form of brain cancer in adults. Despite the use of multiple treatment strategies, the prognosis remains poor. For nearly 2 decades, the standard treatment of patients with GB consists of surgery followed by radiochemotherapy that results in median overall survival time only up to 14.6 months 1. Unfortunately, almost all GB patients experience rapid tumour recurrence, and there is no established standard of care for disease progression after radiotherapy and concomitant temozolomide. Lomustine, a
Seminars in Reproductive Medicine, Jan 22, 2024
► immunome ► microbiome ► reproductive health ► phage immunoprecipitation sequencing ► microbial ... more ► immunome ► microbiome ► reproductive health ► phage immunoprecipitation sequencing ► microbial flow cytometry ► next-generation sequencing ► diagnostic tools ► therapeutic interventions ► interactions
ExplORRNet: An interactive web tool to explore stage-wise miRNA expression profiles and their interactions with mRNA and lncRNA in human breast and gynecological cancers
Non-coding RNA Research, Feb 29, 2024
Journal of assisted reproduction and genetics, Feb 15, 2024
Purpose Ovarian tissue cryopreservation is vital for fertility preservation, yet its effect on ov... more Purpose Ovarian tissue cryopreservation is vital for fertility preservation, yet its effect on ovarian tissue follicle survival and transcriptomic signature requires further investigation. This study delves into the effects of vitrification on tissue morphology, function, and transcriptomic changes, helping to find possibilities for vitrification protocol improvements. Methods Ovarian cortex from 19 bovine animals were used to conduct pre-and post-vitrification culture followed by histological assessment, immunohistochemistry, and TUNEL assay. Follicles' functionality was assessed for viability and growth within the tissue and in isolated cultures. RNA-sequencing of ovarian tissue was used to explore the transcriptomic alterations caused by vitrification. Results Follicle density, cell proliferation, and DNA damage in ovarian stroma were unaffected by vitrification. However, vitrified cultured tissue exhibited reduced follicle density of primordial/primary and antral follicles, while freshly cultured tissue manifested reduction of antral follicles. Increased stromal cell proliferation and DNA damage occurred in both groups post-culture. Isolated follicles from vitrified tissue exhibited similar viability to fresh follicles until day 4, after which the survival dropped. RNA-sequencing revealed minor effects of vitrification on transcriptomic signatures, while culture induced significant gene expression changes in both groups. The altered expression of WNT and hormonal regulation pathway genes post-vitrification suggests the molecular targets for vitrification protocol refinement. Conclusion Vitrification minimally affects tissue morphology, follicle density, and transcriptomic signature post-thawing. However, culture revealed notable changes in vitrified tissue samples, including reduced follicle density, decreased isolated follicle survival, and alteration in WNT signalling and ovarian hormonal regulation pathways, highlighted them as possible limitations of the current vitrification protocol.
Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines: onametostat reduces proliferation and viability in both normoxic and hypoxic conditions
The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and... more The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and most glioblastoma patients die from the disease recurrence. Thus, systematic studies in simplified model systems are required to pinpoint the choice of targets for further exploration in clinical settings. Here, we report screening of 5 compounds targeting epigenetic writers or erasers and 6 compounds targeting cell cycle-regulating protein kinases against 3 glioblastoma cell lines following incubation under normoxic or hypoxic conditions. The viability assay indicated that PRMT5 inhibitor onametostat was endowed with high potency under both normoxic and hypoxic conditions in both MGMT-positive and MGMT-negative cell lines. In U-251 MG and U-87 MG cells, onametostat also affected the spheroid formation at concentrations lower than the currently used chemotherapeutic drug lomustine. Furthermore, in T98-G cell line, treatment with onametostat led to dramatic changes in the transcriptome p...
Human Reproduction, Jun 1, 2023
paracrine factors provided by developed germ cells and somatic cells such as Sertoli, peritubular... more paracrine factors provided by developed germ cells and somatic cells such as Sertoli, peritubular and Leydig cells. These microenvironmental factors are modified following pathological condition, such as chemotherapy, which may lead to subfertility or sterility. Different in vitro culture systems were used to induce the development of complete spermatogenesis in vitro; however, this was not yet achieved. Study design, size, duration: Sexually immature mice (7-day-old) were used as normal or were intraperitoneally (i.p) injected with busulfan (45 mg/ kg) to isolate cells from their seminiferous tubules (STs). Cells were enzymatically isolated from the STs of the mice and were cultured in methylcellulose culture system (MCS), as a 3-dimensinal in vitro system. Fresh media without (CT) or with IL-6 were added to the cultures from the beginning, and after two weeks. The cultures were determined after 4 weeks Participants/materials, setting, methods: Isolated cells from the STs were cultured (2x10 5 /well/0.5ml) in MCS that contained StemPro-34 medium, KSR, rEGF, rGDNF, rLIF, and r-bFGF and in the presence/absence of IL-6 (1,10 or 100 pg/ml) and incubated for four weeks in a CO 2 incubator at 37 C. The developed cells and colonies/organoids were examined microscopically and quantified for the development of cells of the different stages of spermatogenesis and Sertoli cells functional markers by immunofluorescence staining (IF) and/or qPCR analyses. Main results and the role of chance: Addition of IL-6 to MCS that contained isolated cells from STs of normal immature mice significantly increased the development of premeiotic cells (VASA), meiotic (BOULE) and meiotic/ postmeiotic cells (ACROSIN) as examined by specific IF and/or qPCR analyses. Addition of IL-6 also differently affected the expression levels of Sertoli cell functionality markers (androgen receptor, androgen binding protein, transferrin, GDNF, FSHR). Furthermore, addition of IL-6 to isolated cells from STs of busulfan-treated immature mice also increased the development of VASA-, BOULE-and ACROSIN-positive cells (as examined by IF and qPCR analyses). However, the effect of IL-6 was more potent in the development of different stages of spermatogenesis in in vitro cultures that contained isolated cells from STs of normal compared busulfan-treated mice. Also, addition of IL-6 distinctly affected the expression levels of Sertoli cell functional markers in cultures of normal and busulfan-treated mice. Limitations, reasons for caution: This in-vitro culture used animal models. The bio-activity of the developed post-meiotic needs to be confirmed Wider implications of the findings: These findings indicate the possible involvement of IL-6 in the development of spermatogenesis in vitro. This effect could be directly on spermatogonial cells and/or through Sertoli cells. Our result could suggest IL-6 as a potential factor to be used in developing future in vitro therapeutic strategies for male fertility preservation Trial registration number: not applicable Abstract citation ID: dead093.771 P-421 Return rates and outcome of fertility preservation in women with cervical cancer.
Users’ Concerns About Endometriosis on Social Media: Sentiment Analysis and Topic Modeling Study (Preprint)
BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more BACKGROUND Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. OBJECTIVE This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. METHODS We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. RESULTS Since 2011, the number of posts and comments has increased steadily. The posts were categorized into 11 categories, and the highest number of posts were related to either asking for information (Question); sharing the experiences (Rant/Vent); or diagnosing and treating endometriosis, especially surgery (Surgery related). Sentiment analysis revealed that 92.09% (42,077/45,693) of posts were associated with negative sentiments, only 2.3% (1053/45,693) expressed positive feelings, and there were no categories with more positive than negative posts. Topic modeling revealed 27 major topics, and the most popular topics were Surgery, Questions/Advice, Diagnosis, and Pain. The Survey/Research topic, which brought together most research-related posts, was the last in terms of posts. CONCLUSIONS Our study shows that posts on social media platforms can provide insights into the concerns of women with endometriosis symptoms. The analysis of the posts confirmed that women with endometriosis have to face negative emotions and pain daily. The large number of posts related to asking questions shows that women do not receive sufficient information from physicians and need community support to cope with the disease. Health care professionals should pay more attention to the symptoms and diagnosis of endometriosis, discuss these topics with patients to reduce their dissatisfaction with doctors, and contribute more to the overall well-being of women with endometriosis. Researchers should also become more involved in social media and share new science-based knowledge regarding endometriosis.
Frontiers in Reproductive Health
IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic cha... more IntroductionThe expression of genes in female reproductive organs is influenced by the cyclic changes in hormone levels during the menstrual cycle. While the molecular changes in the endometrium that facilitate embryo implantation have been extensively studied, there is limited knowledge about the impact of the menstrual cycle on cervical cells. Cervical cells can be easily and routinely collected using a cytobrush during gynecological examination, offering a standardized approach for diagnostic testing. In this study we investigated how the transcriptome of cervical cells changes during the menstrual cycle and assessed the utility of these cells to determine endometrial receptivity.MethodsEndocervical cells were collected with cytobrushes from 16 healthy women at different menstrual cycle phases in natural cycles and from four women undergoing hormonal replacement cycles. RNA sequencing was applied to gain insight into the transcriptome of cervical cells.ResultsTranscriptome analys...
MBMethPred: a computational framework for the accurate classification of childhood medulloblastoma subgroups using data integration and AI-based approaches
Frontiers in Genetics
Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four ... more Childhood medulloblastoma is a malignant form of brain tumor that is widely classified into four subgroups based on molecular and genetic characteristics. Accurate classification of these subgroups is crucial for appropriate treatment, monitoring plans, and targeted therapies. However, misclassification between groups 3 and 4 is common. To address this issue, an AI-based R package called MBMethPred was developed based on DNA methylation and gene expression profiles of 763 medulloblastoma samples to classify subgroups using machine learning and neural network models. The developed prediction models achieved a classification accuracy of over 96% for subgroup classification by using 399 CpGs as prediction biomarkers. We also assessed the prognostic relevance of prediction biomarkers using survival analysis. Furthermore, we identified subgroup-specific drivers of medulloblastoma using functional enrichment analysis, Shapley values, and gene network analysis. In particular, the genes inv...
Users’ Concerns About Endometriosis on Social Media: Sentiment Analysis and Topic Modeling Study
Journal of Medical Internet Research
Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing... more Background Endometriosis is a debilitating and difficult-to-diagnose gynecological disease. Owing to limited information and awareness, women often rely on social media platforms as a support system to engage in discussions regarding their disease-related concerns. Objective This study aimed to apply computational techniques to social media posts to identify discussion topics about endometriosis and to identify themes that require more attention from health care professionals and researchers. We also aimed to explore whether, amid the challenging nature of the disease, there are themes within the endometriosis community that gather posts with positive sentiments. Methods We retrospectively extracted posts from the subreddits r/Endo and r/endometriosis from January 2011 to April 2022. We analyzed 45,693 Reddit posts using sentiment analysis and topic modeling–based methods in machine learning. Results Since 2011, the number of posts and comments has increased steadily. The posts were...
BMC Medicine
Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable feta... more Background Prenatal alcohol exposure (PAE) affects embryonic development, causing a variable fetal alcohol spectrum disorder (FASD) phenotype with neuronal disorders and birth defects. We hypothesize that early alcohol-induced epigenetic changes disrupt the accurate developmental programming of embryo and consequently cause the complex phenotype of developmental disorders. To explore the etiology of FASD, we collected unique biological samples of 80 severely alcohol-exposed and 100 control newborns at birth. Methods We performed genome-wide DNA methylation (DNAm) and gene expression analyses of placentas by using microarrays (EPIC, Illumina) and mRNA sequencing, respectively. To test the manifestation of observed PAE-associated DNAm changes in embryonic tissues as well as potential biomarkers for PAE, we examined if the changes can be detected also in white blood cells or buccal epithelial cells of the same newborns by EpiTYPER. To explore the early effects of alcohol on extraembryo...
Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsi... more Väitekirja elektrooniline versioon ei sisalda publikatsiooneDNA-s sisalduv geneetiline informatsioon annab vajalikud juhised organismi kasvuks ja arenguks. Lisaks DNA nukleotiidsele järjestusele mõjutavad neid protsesse ka DNA-s esinevad modifikatsioonid. Enim uuritud DNA modifikatsioon on DNA metülatsioon, mis tähendab metüülrühma lisamist tsütosiini külge. DNA on tihtilugu metüleeritud regiooniti, moodustades niinimetatud metülatsioonimustreid. Need “mustrid“ osalevad geeniekspressiooni regulatsioonis, lülitades teatud rakkudes geene sisse ja välja või kohandades nende aktiivsust. On oluline märkida, et DNA metülatsioon on tugevalt mõjutatud keskkonnateguritest, nimelt vastavalt keskkonnatingimustele võidakse teatud regioone metüleerida või vastupidi, metüülrühmi eemaldada. Seega on DNA metülatsioon üheks vahelüliks geneetika ja keskkonna vahel. Paljud neist “mustritest“ on omased tavalistele bioloogilistele protsessidele, kuid leidub ka selliseid, mis viitavad haiguse olemasolule...
The expression pattern of endometrial receptivity genes is desynchronized between endometrium and matched endometriomas
Reproductive BioMedicine Online
Next generation sequencing analysis of lung cancer datasets: A functional genomics perspective
Indian Journal of Cancer, 2016
Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epitheli... more Cigarette smoking leads to serious epidemics in humans, creating torsion of infection in epithelial cells lining the respiratory tracts. Several researchers in the recent past have theorized that the next generation sequencing (NGS), especially transcriptome sequencing has enhanced understanding lung cancers and other epithelial epidemics. Conversely, pathogenesis specific to lung cancer with respect to molecular fraction of genomic ribonucleic acid has some mutant effect in various populations like smokers with lung cancer, healthy never smokers and vice versa. We review the impending impact of NGS data while providing insights into the biology of lung cancer affecting various populations, which we believe would be an add-on service for predictive biology approaches. Furthermore, we conclude what would be the outcome of such analysis for Indian population. Bioinformatics analysis was performed using various tools. We identified five genes namely epidermal growth factor receptor, Kirsten rat sarcoma, adenomatosis polyposis down regulated-1, N-ethylmaleimide-sensitive factor attachment protein, gamma and Piezo type mechanosensitive ion channel component 2 whose role was implicated in lung cancer and further analysis has to be performed to check whether or not the genes are indeed completely involved in causing lung cancer.
Glycobiology, 2009
ECODAB (the E. coli O-antigen database) has been expanded to include information about glycosyltr... more ECODAB (the E. coli O-antigen database) has been expanded to include information about glycosyltransferases (GTs) involved in the assembly of the O-antigen polysaccharide. Similarity searches have been performed to be able to determine GT functions that have not been reported prior to this work. In addition to suggesting the function of 179 GTs, the approach leads to the prediction of part of the O-antigen structures of a number of serogroups. The procedure suggests a novel way of combining genetic information with experimental techniques in structural analysis of oligoand polysaccharides.
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Papers by Vijayachitra Modhukur