'; ?> geneimprint : Hot off the Press http://www.geneimprint.com/site/hot-off-the-press Daily listing of the most recent articles in epigenetics and imprinting, collected from the PubMed database. en-us Wed, 22 May 2019 12:27:16 EDT Wed, 22 May 2019 12:27:16 EDT jirtle@radonc.duke.edu james001@jirtle.com De Novo DNA Methylation at Imprinted Loci during Reprogramming into Naive and Primed Pluripotency. Yagi M, Kabata M, Ukai T, Ohta S, Tanaka A, Shimada Y, Sugimoto M, Araki K, Okita K, Woltjen K, Hochedlinger K, Yamamoto T, Yamada Y
Stem Cell Reports (May 2019)

CpG islands (CGIs) including those at imprinting control regions (ICRs) are protected from de novo methylation in somatic cells. However, many cancers often exhibit CGI hypermethylation, implying that the machinery is impaired in cancer cells. Here, we conducted a comprehensive analysis of CGI methylation during somatic cell reprogramming. Although most CGIs remain hypomethylated, a small subset of CGIs, particularly at several ICRs, was often de novo methylated in reprogrammed pluripotent stem cells (PSCs). Such de novo ICR methylation was linked with the silencing of reprogramming factors, which occurs at a late stage of reprogramming. The ICR-preferred CGI hypermethylation was similarly observed in human PSCs. Mechanistically, ablation of Dnmt3a prevented PSCs from de novo ICR methylation. Notably, the ICR-preferred CGI hypermethylation was observed in pediatric cancers, while adult cancers exhibit genome-wide CGI hypermethylation. These results may have important implications in the pathogenesis of pediatric cancers and the application of PSCs.]]>
Wed, 31 Dec 1969 19:00:00 EST
An ATAC-seq atlas of chromatin accessibility in mouse tissues. Liu C, Wang M, Wei X, Wu L, Xu J, Dai X, Xia J, Cheng M, Yuan Y, Zhang P, Li J, Feng T, Chen A, Zhang W, Chen F, Shang Z, Zhang X, Peters BA, Liu L
Sci Data (May 2019)

The Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) is a fundamental epigenomics approach and has been widely used in profiling the chromatin accessibility dynamics in multiple species. A comprehensive reference of ATAC-seq datasets for mammalian tissues is important for the understanding of regulatory specificity and developmental abnormality caused by genetic or environmental alterations. Here, we report an adult mouse ATAC-seq atlas by producing a total of 66 ATAC-seq profiles from 20 primary tissues of both male and female mice. The ATAC-seq read enrichment, fragment size distribution, and reproducibility between replicates demonstrated the high quality of the full dataset. We identified a total of 296,574 accessible elements, of which 26,916 showed tissue-specific accessibility. Further, we identified key transcription factors specific to distinct tissues and found that the enrichment of each motif reflects the developmental similarities across tissues. In summary, our study provides an important resource on the mouse epigenome and will be of great importance to various scientific disciplines such as development, cell reprogramming, and genetic disease.]]>
Wed, 31 Dec 1969 19:00:00 EST
Toxicogenomics - What added Value Do These Approaches Provide for Carcinogen Risk Assessment? Schmitz-Spanke S
Environ Res (Jun 2019)

It is still a major challenge to protect humans at workplaces and in the environment. To cope with this task, it is a prerequisite to obtain detailed information on the extent of chemical perturbations of biological pathways, in particular, adaptive vs. adverse effects and the dose-response relationships. This knowledge serves as the basis for the classification of non-carcinogens and carcinogens and for further distinguishing carcinogens in genotoxic (DNA damaging) or non-genotoxic compounds. Basing on quantitative dose-response relationships, points of departures can be derived for chemical risk assessment. In recent years, new methods have shown their capability to support the established rodent models of carcinogenicity testing. In vitro high throughput screening assays assess more comprehensively cell response. In addition, omics technologies were applied to study the mode of action of chemicals whereby the term "toxicogenomics" comprises various technologies such as transcriptomics, epigenomics, or metabolomics. This review aims to summarize the current state of toxicogenomic approaches in risk science and to compare them with established ones. For example, measurement of global transcriptional changes generates meaningful information for toxicological risk assessment such as accurate classification of genotoxic/non-genotoxic carcinogens. Alteration in mRNA expression offers previously unknown insights in the mode of action and enables the definition of key events. Based on these, benchmark doses can be calculated for the transition from an adaptive to an adverse state. In short, this review assesses the potential and challenges of transcriptomics and addresses the impact of other omics technologies on risk assessment in terms of hazard identification and dose-response assessment.]]>
Wed, 31 Dec 1969 19:00:00 EST
An integrative association method for omics data based on a modified Fisher's method with application to childhood asthma. Yan Q, Liu N, Forno E, Canino G, Celedón JC, Chen W
PLoS Genet (May 2019)

The development of high-throughput biotechnologies allows the collection of omics data to study the biological mechanisms underlying complex diseases at different levels, such as genomics, epigenomics, and transcriptomics. However, each technology is designed to collect a specific type of omics data. Thus, the association between a disease and one type of omics data is usually tested individually, but this strategy is suboptimal. To better articulate biological processes and increase the consistency of variant identification, omics data from various platforms need to be integrated. In this report, we introduce an approach that uses a modified Fisher's method (denoted as Omnibus-Fisher) to combine separate p-values of association testing for a trait and SNPs, DNA methylation markers, and RNA sequencing, calculated by kernel machine regression into an overall gene-level p-value to account for correlation between omics data. To consider all possible disease models, we extend Omnibus-Fisher to an optimal test by using perturbations. In our simulations, a usual Fisher's method has inflated type I error rates when directly applied to correlated omics data. In contrast, Omnibus-Fisher preserves the expected type I error rates. Moreover, Omnibus-Fisher has increased power compared to its optimal version when the true disease model involves all types of omics data. On the other hand, the optimal Omnibus-Fisher is more powerful than its regular version when only one type of data is causal. Finally, we illustrate our proposed method by analyzing whole-genome genotyping, DNA methylation data, and RNA sequencing data from a study of childhood asthma in Puerto Ricans.]]>
Wed, 31 Dec 1969 19:00:00 EST
The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. Rimassa L, Personeni N, Aghemo A, Lleo A
J Autoimmun (Jun 2019)

Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown. CCA is characterized by a highly desmoplastic microenvironment containing stromal cells, mainly cancer-associated fibroblasts, infiltrating tumor epithelium. Tumor microenvironment in CCA is a highly dynamic environment that, besides stromal and endothelial cells, encompass also an abundance of immune cells, of both the innate and adaptive immune system (including tumor-associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes) and abundant proliferative factors. It is orchestrated by multiple soluble factors and signals, that eventually define a tumor growth-permissive microenvironment. Through complicate interactions with CCA cells, tumor microenvironment profoundly affects the proliferative and invasive abilities of epithelial cancer cells and plays an important role in accelerating neovascularization and preventing apoptosis of neoplastic cells. In this review, we discuss recent developments regarding the characteristics of the tumor microenvironment, the role of each cellular population, and their multiarticulate interaction with the malignant population. Further we discuss innovative treatment approaches, including immunotherapy, and how identification of CCA secreted factors by both the stromal component and immune cell subsets are leading towards a precision medicine in CCA.]]>
Wed, 31 Dec 1969 19:00:00 EST
2017 WONOEP appraisal: Studying epilepsy as a network disease using systems biology approaches. Mahoney JM, Mills JD, Muhlebner A, Noebels J, Potschka H, Simonato M, Kobow K
Epilepsia (May 2019)

The revolution in high-throughput omics technologies has dramatically expanded our understanding of the epilepsies as complex diseases. It is now clear that further progress in treating the full spectrum of seizure disorders requires a systems-level framework for analyzing and integrating data from multiple omics technologies that moves beyond the search for single molecular alterations to an understanding of dysregulated pathways in epilepsy. Taking such a pathway-centered view requires further integrating the tools of systems biology into epilepsy research. In this appraisal, we highlight and summarize systems biology approaches in basic epilepsy studies as they were discussed during the 2017 Workshop on the Neurobiology of Epilepsy (WONOEP). During the 3-day event, participants exchanged emerging results and thoughts on developing the systems biology of epilepsy, and the promise and limitations of these approaches for the near term.]]>
Wed, 31 Dec 1969 19:00:00 EST
Genetics and Epigenetics of Infertility and Treatments on Outcomes. Pisarska MD, Chan JL, Lawrenson K, Gonzalez TL, Wang ET
J Clin Endocrinol Metab (Jun 2019)

Infertility affects 10% of the reproductive-age population. Even the most successful treatments such as assisted reproductive technologies still result in failed implantation. In addition, adverse pregnancy outcomes associated with infertility have been attributed to these fertility treatments owing to the presumed epigenetic modifications of in vitro fertilization and in vitro embryo development. However, the diagnosis of infertility has been associated with adverse outcomes, and the etiologies leading to infertility have been associated with adverse pregnancy and long-term outcomes.]]>
Wed, 31 Dec 1969 19:00:00 EST
"Omics" Education in Dietetic Curricula: A Comparison between Two Institutions in the USA and Mexico. VanBuren C, Imrhan V, Vijayagopal P, Solis-Pérez E, López-Cabanillas Lomelí M, Gonzalez-Garza R, Gutiérrez-López M, González-Martinez BE, Boonme K, Juma S, Prasad C
Lifestyle Genom (May 2019)

The completion of sequencing of the human genome and a better understanding of epigenomic regulation of gene expression have opened the possibility of personalized nutrition in the near future. This has also created an immediate need for trained personnel qualified to administer personalized nutrition education. Of all the allied healthcare personnel, dietitians are the most likely to undertake this role. However, dietitians and dietetic students are still deficient in their knowledge of nutrigenomics and other "omics" technologies. Therefore, with the eventual goal of dietetic curriculum reorganization, the International Society of Nutrigenetics/Nutrigenomics (ISNN) has set out to evaluate nutrigenomic knowledge among dietetic students from different countries. In this study, we compared nutrition and dietetic students from Texas Woman's University (TWU) and the Universidad Autónoma de Nuevo León (UANL) for their perceived need for, interest in, and knowledge of different topics within nutritional genomics.]]>
Wed, 31 Dec 1969 19:00:00 EST
Paternally Expressed Imprinted Genes under Positive Darwinian Selection in Arabidopsis thaliana. Tuteja R, McKeown PC, Ryan P, Morgan CC, Donoghue MTA, Downing T, O'Connell MJ, Spillane C
Mol Biol Evol (06 2019)

Genomic imprinting is an epigenetic phenomenon where autosomal genes display uniparental expression depending on whether they are maternally or paternally inherited. Genomic imprinting can arise from parental conflicts over resource allocation to the offspring, which could drive imprinted loci to evolve by positive selection. We investigate whether positive selection is associated with genomic imprinting in the inbreeding species Arabidopsis thaliana. Our analysis of 140 genes regulated by genomic imprinting in the A. thaliana seed endosperm demonstrates they are evolving more rapidly than expected. To investigate whether positive selection drives this evolutionary acceleration, we identified orthologs of each imprinted gene across 34 plant species and elucidated their evolutionary trajectories. Increased positive selection was sought by comparing its incidence among imprinted genes with nonimprinted controls. Strikingly, we find a statistically significant enrichment of imprinted paternally expressed genes (iPEGs) evolving under positive selection, 50.6% of the total, but no such enrichment for positive selection among imprinted maternally expressed genes (iMEGs). This suggests that maternally- and paternally expressed imprinted genes are subject to different selective pressures. Almost all positively selected amino acids were fixed across 80 sequenced A. thaliana accessions, suggestive of selective sweeps in the A. thaliana lineage. The imprinted genes under positive selection are involved in processes important for seed development including auxin biosynthesis and epigenetic regulation. Our findings support a genomic imprinting model for plants where positive selection can affect paternally expressed genes due to continued conflict with maternal sporophyte tissues, even when parental conflict is reduced in predominantly inbreeding species.]]>
Wed, 31 Dec 1969 19:00:00 EST
Next generation sequencing data for use in risk assessment. Merrick BA
Curr Opin Toxicol (Dec 2019)

Next generation sequencing (NGS) represents several powerful platforms that have revolutionized RNA and DNA analysis. The parallel sequencing of millions of DNA molecules can provide mechanistic insights into toxicology and provide new avenues for biomarker discovery with growing relevance for risk assessment. The evolution of NGS technologies has improved over the last decade with increased sensitivity and accuracy to foster new biomarker assays from tissue, blood and other biofluids. NGS sequencing technologies can identify transcriptional changes and genomic targets with base pair precision in response to chemical exposure. Further, there are several exciting movements within the toxicology community that incorporate NGS platforms into new strategies for more rapid toxicological characterizations. These include the Tox21 in vitro high throughput transcriptomic screening program, development of organotypic spheroids, alternative animal models, mining archival tissues, liquid biopsy and epigenomics. This review will describe NGS-based technologies, demonstrate how they can be used as tools for target discovery in tissue and blood, and suggest how they might be applied for risk assessment.]]>
Wed, 31 Dec 1969 19:00:00 EST
Epigenetics and epigenomics in diabetic kidney disease and metabolic memory. Kato M, Natarajan R
Nat Rev Nephrol (Jun 2019)

The development and progression of diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, are influenced by both genetic and environmental factors. DKD is an important contributor to the morbidity of patients with diabetes mellitus, indicating a clear need for an improved understanding of disease aetiology to inform the development of more efficacious treatments. DKD is characterized by an accumulation of extracellular matrix, hypertrophy and fibrosis in kidney glomerular and tubular cells. Increasing evidence shows that genes associated with these features of DKD are regulated not only by classical signalling pathways but also by epigenetic mechanisms involving chromatin histone modifications, DNA methylation and non-coding RNAs. These mechanisms can respond to changes in the environment and, importantly, might mediate the persistent long-term expression of DKD-related genes and phenotypes induced by prior glycaemic exposure despite subsequent glycaemic control, a phenomenon called metabolic memory. Detection of epigenetic events during the early stages of DKD could be valuable for timely diagnosis and prompt treatment to prevent progression to end-stage renal disease. Identification of epigenetic signatures of DKD via epigenome-wide association studies might also inform precision medicine approaches. Here, we highlight the emerging role of epigenetics and epigenomics in DKD and the translational potential of candidate epigenetic factors and non-coding RNAs as biomarkers and drug targets for DKD.]]>
Wed, 31 Dec 1969 19:00:00 EST
Origins of DNA methylation defects in Wilms tumors. Anvar Z, Acurzio B, Roma J, Cerrato F, Verde G
Cancer Lett (May 2019)

Wilms tumor is an embryonic renal cancer that typically presents in early childhood and accounts for 7% of all pediatric cancers. Different genetic alterations have been described in this malignancy, however, only a few of them are associated with a majority of Wilms tumors. Alterations in DNA methylation, in contrast, are frequent molecular defects observed in most cases of Wilms tumors. How these methylation alterations are established in this tumor is not yet completely clear. The recent identification of the molecular actors required for the epigenetic reprogramming during embryogenesis suggest novel possible mechanisms responsible for the DNA methylation defects in Wilms tumor. Here, we provide an overview of the DNA methylation alterations observed in this malignancy and discuss the distinct molecular mechanisms by which these epimutations can arise.]]>
Wed, 31 Dec 1969 19:00:00 EST
One protein to rule them all: The role of CCCTC-binding factor in shaping human genome in health and disease. Lazniewski M, Dawson WK, Rusek AM, Plewczynski D
Semin Cell Dev Biol (Jun 2019)

The eukaryotic genome, constituting several billion base pairs, must be contracted to fit within the volume of a nucleus where the diameter is on the scale of μm. The 3D structure and packing of such a long sequence cannot be left to pure chance, as DNA must be efficiently used for its primary roles as a matrix for transcription and replication. In recent years, methods like chromatin conformation capture (including 3C, 4C, Hi-C, ChIA-PET and Multi-ChIA) and optical microscopy have advanced substantially and have shed new light on how eukaryotic genomes are hierarchically organized; first into 10-nm fiber, next into DNA loops, topologically associated domains and finally into interphase or mitotic chromosomes. This knowledge has allowed us to revise our understanding regarding the mechanisms governing the process of DNA organization. Mounting experimental evidence suggests that the key element in the formation of loops is the binding of the CCCTC-binding factor (CTCF) to DNA; a protein that can be referred to as the chief organizer of the genome. However, CTCF does not work alone but in cooperation with other proteins, such as cohesin or Yin Yang 1 (YY1). In this short review, we briefly describe our current understanding of the structure of eukaryotic genomes, how they are established and how the formation of DNA loops can influence gene expression. We discuss the recent discoveries describing the 3D structure of the CTCF-DNA complex and the role of CTCF in establishing genome structure. Finally, we briefly explain how various genetic disorders might arise as a consequence of mutations in the CTCF target sequence or alteration of genomic imprinting.]]>
Wed, 31 Dec 1969 19:00:00 EST
Prader-Willi syndrome imprinting centre deletion mice have impaired baseline and 5-HT2CR-mediated response inhibition. Davies JR, Wilkinson LS, Isles AR, Humby T
Hum Mol Genet (May 2019)

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by deletion or inactivation of paternally expressed imprinted genes on human chromosome 15q11-q13. In addition to endocrine and developmental issues, PWS presents with behavioural problems including stereotyped behaviour, impulsiveness and cognitive deficits. The PWS genetic interval contains several brain-expressed small nucleolar (sno)RNA species that are subject to genomic imprinting, including snord115 which negatively regulates post-transcriptional modification of the serotonin 2C receptor (5-HT2CR) pre-mRNA potentially leading to a reduction in 5-HT2CR function. Using the imprinting centre (IC) deletion mouse model for PWS (PWSICdel) we have previously shown impairments in a number of behaviours, some of which are abnormally sensitive to 5-HT2CR-selective drugs. In the stop-signal reaction time task test of impulsivity, PWSICdel mice showed increased impulsivity relative to wild-type littermates. Challenge with the selective 5-HT2CR agonist WAY163909 reduced impulsivity in PWSICdel mice but had no effect on wild-type behaviour. This behavioural dissociation in was also reflected in differential patterns of immunoreactivity of the immediate early gene c-Fos, with a blunted response to the drug in the orbitofrontal cortex of PWSICdel mice, but no difference in c-Fos activation in the nucleus accumbens. These findings suggest specific facets of response inhibition are impaired in PWSICdel mice and that abnormal 5-HT2CR function may mediate this dissociation. These data have implications for our understanding of the aetiology of PWS related behavioural traits and translational relevance for individuals with PWS who may seek to control appetite with the new obesity treatment 5-HT2CR agonist lorcaserin.]]>
Wed, 31 Dec 1969 19:00:00 EST
Roles of CTCF in conformation and functions of chromosome. Liu F, Wu D, Wang X
Semin Cell Dev Biol (Jun 2019)

CCCTC-binding factor (CTCF) plays indispensable roles in transcriptional inhibition/activation, insulation, gene imprinting, and regulation of 3Dchromatin structure. CTCF contributes to formation of genome multi-dimensions, regulation of dimensional changes, or control of central signals to transcriptional networks. A large number of factors affect CTCF binding, methylation/demethylation, base mutation, or poly(adp-ribosyl)ation. CTCF is one of the most important elements in the regulation of chromatin folding by combining with CBSs in TADs in a positive-reverse or reverse-positive orders. CTCF acts as a versatile nuclear factor, a transcriptional activator or repressor, an insulator binding factor, or a regulator of genomic imprinting as required for various biological procedures. Although molecular regulatory mechanisms of CTCF in cell differentiation and disease development remains unclear, roles of CTCF in carcinogenesis have been intensively explored. There is little understanding about regulatory roles of CTCF in inflammation-associated transcriptional signaling, cell injury, organ dysfunction, and systemic responses. It is also highly expected that further in-depth studies of CTCF control mechanisms can provide better understanding of disease development and potential disease-specific biomarkers and therapeutic targets.]]>
Wed, 31 Dec 1969 19:00:00 EST
Improved Detection of Epigenomic Marks With Mixed Effects Hidden Markov Models. Baldoni PL, Rashid NU, Ibrahim JG
Biometrics (May 2019)

Chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) is a technique to detect genomic regions containing protein-DNA interaction, such as transcription factor binding sites or regions containing histone modifications. One goal of the analysis of ChIP-seq experiments is to identify genomic loci enriched for sequencing reads pertaining to DNA bound to the factor of interest. The accurate identification of such regions aids in the understanding of epigenomic marks and gene regulatory mechanisms. Given the reduction of massively parallel sequencing costs, methods to detect consensus regions of enrichment across multiple samples are of interest. Here, we present a statistical model to detect broad consensus regions of enrichment from ChIP-seq technical or biological replicates through a class of Zero-Inflated Mixed Effects Hidden Markov Models. We show that the proposed model outperforms existing methods for consensus peak calling in common epigenomic marks by accounting for the excess zeros and sample-specific biases. We apply our method to data from the Encyclopedia of DNA Elements (ENCODE) and Roadmap Epigenomics projects and also from an extensive simulation study. This article is protected by copyright. All rights reserved.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multidimensional Single-Cell Analyses in Organ Development and Maintenance. Zhang Y, Liu F
Trends Cell Biol (Jun 2019)

The revolution of single-cell analysis tools in epigenomics, transcriptomics, lineage tracing, and transcriptome-scale RNA imaging, has boosted our understanding of the underlying molecular mechanisms during organ development and maintenance. Application of these tools enables the multidimensional study of organs, from cell atlas profiling, spatial organization, to cell-cell interaction. Here, we discuss recent progress in employing multidimensional single-cell analyses to address fundamental questions related to the development and maintenance of hematopoietic organs, brain and lung, which will also help provide insights into a better understanding of relevant diseases.]]>
Wed, 31 Dec 1969 19:00:00 EST
Regulation of Parent-of-Origin Allelic Expression in the Endosperm. Hornslien KS, Miller JR, Grini PE
Plant Physiol (May 2019)

Genomic imprinting is an epigenetic phenomenon established in the gametes prior to fertilization that causes differential expression of parental alleles, mainly in the endosperm of flowering plants. The overlap between previously identified panels of imprinted genes is limited. To investigate imprinting, we used high-resolution sequencing data acquired with sequence capture technology. We present a bioinformatics pipeline to assay parent-of-origin allele-specific expression and report more than 300 loci with parental expression bias in Arabidopsis thaliana. In most cases, the level of expression from maternal and paternal alleles was not binary, instead supporting a differential dosage hypothesis for the evolution of imprinting in plants. To address imprinting regulation, we systematically employed mutations in regulative epigenetic pathways suggested to be major players in the process. We established the mechanistic mode of imprinting for more than 50 loci regulated by DNA methylation and Polycomb-dependent histone methylation. However, the imprinting patterns of most genes were not affected by these mechanisms. To this end, we also demonstrated that the RNA-directed DNA methylation pathway alone does not substantially influence imprinting patterns, suggesting that more complex epigenetic pathways regulate most of the identified imprinted genes.]]>
Wed, 31 Dec 1969 19:00:00 EST
Multi-network approach to identify differentially methylated gene communities in cancer. R V, Nazeer KAA
Gene (May 2019)

High-throughput Next Generation Sequencing tools have generated immense quantity of genome-wide methylation and expression profiling data, resulting in an unprecedented opportunity to unravel the epigenetic regulatory mechanisms underlying cancer. Identifying differentially methylated regions within gene networks is an important step towards revealing the cancer epigenome blueprint. Approaches that integrate gene methylation and expression profiles assume their negative correlation and build a single scaffold network to cluster. However, the exact regulatory mechanism between gene expression and methylation is not precisely deciphered.]]>
Wed, 31 Dec 1969 19:00:00 EST
Protocol for a scoping review of multi-omic analysis for rare diseases. Kerr K, McAneney H, McKnight AJ
BMJ Open (May 2019)

The development of next generation sequencing technology has enabled cost-efficient, large scale, multiple 'omic' analysis, including epigenomic, genomic, metabolomic, phenomic, proteomic and transcriptomic research. These integrated approaches hold significant promise for rare disease research, with the potential to aid biomarker discovery, improve our understanding of disease pathogenesis and identify novel therapeutic targets. In this paper we outline a systematic approach for a scoping review designed to evaluate what primary research has been performed to date on multi-omics and rare disease.]]>
Wed, 31 Dec 1969 19:00:00 EST