Abstract
While long non-coding RNA (lncRNA) research in the past has primarily focused on the discovery of novel genes, today it has shifted towards functional annotation of this large class of ...genes. With thousands of lncRNA studies published every year, the current challenge lies in keeping track of which lncRNAs are functionally described. This is further complicated by the fact that lncRNA nomenclature is not straightforward and lncRNA annotation is scattered across different resources with their own quality metrics and definition of a lncRNA. To overcome this issue, large scale curation and annotation is needed. Here, we present the fifth release of the human lncRNA database LNCipedia (https://lncipedia.org). The most notable improvements include manual literature curation of 2482 lncRNA articles and the use of official gene symbols when available. In addition, an improved filtering pipeline results in a higher quality reference lncRNA gene set.
One hundred years of insulin therapy Mathieu, Chantal; Martens, Pieter-Jan; Vangoitsenhoven, Roman
Nature reviews. Endocrinology,
12/2021, Volume:
17, Issue:
12
Journal Article
Peer reviewed
At the time of its first clinical application 100 years ago, insulin was presented as the cure for people with diabetes mellitus. That transpired to be an overstatement, yet insulin has proven to be ...the lifesaver for people with type 1 diabetes mellitus and an essential therapy for many with type 2 diabetes mellitus or other forms of diabetes mellitus. Since its discovery, insulin (a molecule of only 51 amino acids) has been the subject of pharmaceutical research and development that has paved the way for other protein-based therapies. From purified animal-extracted insulin and human insulin produced by genetically modified organisms to a spectrum of insulin analogues, pharmaceutical laboratories have strived to tailor the preparations to the needs of patients. Nonetheless, overall glycaemic control often remains poor as exogenous insulin is still not able to mimic the physiological insulin profile. Circumventing subcutaneous administration and the design of analogues with profiles that mimic that of physiological insulin are ongoing areas of research. Novel concepts, such as once-weekly insulins or glucose-dependent and oral insulins, are on the horizon but their real-world effectiveness still needs to be proven. Until a true cure for type 1 diabetes mellitus is found and the therapeutic arsenal for other forms of diabetes mellitus is expanded, insulin will remain central in the treatment of many people living with diabetes mellitus.
Ever since its discovery by Windhaus, the importance of the active metabolite of vitamin D (1,25-dihydroxyvitamin D
; 1,25-(OH)2D
) has been ever expanding. In this review, the attention is shifted ...towards the importance of the extra-skeletal effects of vitamin D, with special emphasis on the immune system. The first hint of the significant role of vitamin D on the immune system was made by the discovery of the presence of the vitamin D receptor on almost all cells of the immune system. In vitro, the overwhelming effect of supra-physiological doses of vitamin D on the individual components of the immune system is very clear. Despite these promising pre-clinical results, the translation of the in vitro observations to solid clinical effects has mostly failed. Nevertheless, the evidence of a link between vitamin D deficiency and adverse outcomes is overwhelming and clearly points towards avoidance of vitamin D deficiency especially in early life.
The placenta is the interface between mother and fetus and inadequate function contributes to short and long-term ill-health. The placenta is absent from most large-scale RNA-Seq datasets. We ...therefore analyze long and small RNAs (~101 and 20 million reads per sample respectively) from 302 human placentas, including 94 cases of preeclampsia (PE) and 56 cases of fetal growth restriction (FGR). The placental transcriptome has the seventh lowest complexity of 50 human tissues: 271 genes account for 50% of all reads. We identify multiple circular RNAs and validate 6 of these by Sanger sequencing across the back-splice junction. Using large-scale mass spectrometry datasets, we find strong evidence of peptides produced by translation of two circular RNAs. We also identify novel piRNAs which are clustered on Chr1 and Chr14. PE and FGR are associated with multiple and overlapping differences in mRNA, lincRNA and circRNA but fewer consistent differences in small RNAs. Of the three protein coding genes differentially expressed in both PE and FGR, one encodes a secreted protein FSTL3 (follistatin-like 3). Elevated serum levels of FSTL3 in pregnant women are predictive of subsequent PE and FGR. To aid visualization of our placenta transcriptome data, we develop a web application ( https://www.obgyn.cam.ac.uk/placentome/ ).
The human genome is pervasively transcribed, producing thousands of non-coding RNA transcripts. The majority of these transcripts are long non-coding RNAs (lncRNAs) and novel lncRNA genes are being ...identified at rapid pace. To streamline these efforts, we created LNCipedia, an online repository of lncRNA transcripts and annotation. Here, we present LNCipedia 3.0 (http://www.lncipedia.org), the latest version of the publicly available human lncRNA database. Compared to the previous version of LNCipedia, the database grew over five times in size, gaining over 90,000 new lncRNA transcripts. Assessment of the protein-coding potential of LNCipedia entries is improved with state-of-the art methods that include large-scale reprocessing of publicly available proteomics data. As a result, a high-confidence set of lncRNA transcripts with low coding potential is defined and made available for download. In addition, a tool to assess lncRNA gene conservation between human, mouse and zebrafish has been implemented.
Accumulating evidence highlights the role of long non-coding RNAs (lncRNAs) in cellular homeostasis, and their dysregulation in disease settings. Most lncRNAs function by interacting with proteins or ...protein complexes. While several orthogonal methods have been developed to identify these proteins, each method has its inherent strengths and limitations. Here, we combine two RNA-centric methods ChIRP-MS and RNA-BioID to obtain a comprehensive list of proteins that interact with the well-known lncRNA HOTAIR. Overexpression of HOTAIR has been associated with a metastasis-promoting phenotype in various cancers. Although HOTAIR is known to bind with PRC2 and LSD1 protein complexes, only very limited unbiased comprehensive approaches to map its interactome have been performed. Both ChIRP-MS and RNA-BioID data sets show an association of HOTAIR with mitoribosomes, suggesting that HOTAIR has functions independent of its (post-)transcriptional mode-of-action.
Trials involving Asian patients with acute stroke have suggested that endovascular treatment alone is not inferior to the usual practice of thrombolysis before endovascular treatment. This trial ...involving European patients did not show noninferiority or superiority of endovascular treatment alone.
Discovery of variant peptides such as a single amino acid variant (SAAV) in shotgun proteomics data is essential for personalized proteomics. Both the resolution of shotgun proteomics methods and the ...search engines have improved dramatically, allowing for confident identification of SAAV peptides. However, it is not yet known if these methods are truly successful in accurately identifying SAAV peptides without prior genomic information in the search database. We studied this in unprecedented detail by exploiting publicly available long-read RNA sequences and shotgun proteomics data from the gold standard reference cell line NA12878. Searching spectra from this cell line with the state-of-the-art open modification search engine ionbot against carefully curated search databases resulted in 96.7% false-positive SAAVs and an 85% lower true positive rate than searching with peptide search databases that incorporate prior genetic information. While adding genetic variants to the search database remains indispensable for correct peptide identification, inclusion of long-read RNA sequences in the search database contributes only 0.3% new peptide identifications. These findings reveal the differences in SAAV detection that result from various approaches, providing guidance to researchers studying SAAV peptides and developers of peptide spectrum identification tools.
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