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      Activation of Transposable Elements in Immune Cells of Fibromyalgia Patients

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          Abstract

          Advancements in nucleic acid sequencing technology combined with an unprecedented availability of metadata have revealed that 45% of the human genome constituted by transposable elements (TEs) is not only transcriptionally active but also physiologically necessary. Dysregulation of TEs, including human retroviral endogenous sequences (HERVs) has been shown to associate with several neurologic and autoimmune diseases, including Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, no study has yet addressed whether abnormal expression of these sequences correlates with fibromyalgia (FM), a disease frequently comorbid with ME/CFS. The work presented here shows, for the first time, that, in fact, HERVs of the H, K and W types are overexpressed in immune cells of FM patients with or without comorbid ME/CFS. Patients with increased HERV expression (N = 14) presented increased levels of interferon (INF-β and INF-γ) but unchanged levels of TNF-α. The findings reported in this study could explain the flu-like symptoms FM patients present with in clinical practice, in the absence of concomitant infections. Future work aimed at identifying specific genomic loci differentially affected in FM and/or ME/CFS is warranted.

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          Most cited references52

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          The Dfam database of repetitive DNA families

          Repetitive DNA, especially that due to transposable elements (TEs), makes up a large fraction of many genomes. Dfam is an open access database of families of repetitive DNA elements, in which each family is represented by a multiple sequence alignment and a profile hidden Markov model (HMM). The initial release of Dfam, featured in the 2013 NAR Database Issue, contained 1143 families of repetitive elements found in humans, and was used to produce more than 100 Mb of additional annotation of TE-derived regions in the human genome, with improved speed. Here, we describe recent advances, most notably expansion to 4150 total families including a comprehensive set of known repeat families from four new organisms (mouse, zebrafish, fly and nematode). We describe improvements to coverage, and to our methods for identifying and reducing false annotation. We also describe updates to the website interface. The Dfam website has moved to http://dfam.org. Seed alignments, profile HMMs, hit lists and other underlying data are available for download.
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            The fibromyalgia impact questionnaire: development and validation.

            An instrument has been developed to assess the current health status of women with the fibromyalgia syndrome. The Fibromyalgia Impact Questionnaire (FIQ) is a brief 10-item, self-administered instrument that measures physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being. We describe its development and validation. This initial assessment indicates that the FIQ has sufficient evidence of reliability and validity to warrant further testing in both research and clinical situations.
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              TEtranscripts: a package for including transposable elements in differential expression analysis of RNA-seq datasets.

              Most RNA-seq data analysis software packages are not designed to handle the complexities involved in properly apportioning short sequencing reads to highly repetitive regions of the genome. These regions are often occupied by transposable elements (TEs), which make up between 20 and 80% of eukaryotic genomes. They can contribute a substantial portion of transcriptomic and genomic sequence reads, but are typically ignored in most analyses.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 February 2020
                February 2020
                : 21
                : 4
                : 1366
                Affiliations
                [1 ]School of Medicine, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain; tamara.ovejero@ 123456ucv.es
                [2 ]Université de Poitiers, CEDEX, 86073 Poitiers, France; sadonesoceane@ 123456gmail.com
                [3 ]Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, 46008 Valencia, Spain; mt.sanchez@ 123456ucv.es (T.S.-F.); eloy.almenar@ 123456ucv.es (E.A.-P.)
                [4 ]School of Biotechnology, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain; joseandres.espejo@ 123456mail.ucv.es
                [5 ]National Health Service, Manises Hospital, 46940 Valencia, Spain; evamariamartinmartinez@ 123456gmail.com
                [6 ]Institute for Neuro Immune Medicine, Nova Southeastern University, Ft Lauderdale, FL 33314, USA; lnathanson@ 123456nova.edu
                [7 ]Centro de Investigación Traslacional San Alberto Magno, Universidad Católica de Valencia San Vicente Mártir, 46001 Valencia, Spain
                Author notes
                [* ]Correspondence: elisa.oltra@ 123456ucv.es ; Tel.:+34-963637412
                Author information
                https://orcid.org/0000-0002-5042-9724
                https://orcid.org/0000-0001-8877-0197
                https://orcid.org/0000-0003-1038-9083
                https://orcid.org/0000-0003-0598-2907
                Article
                ijms-21-01366
                10.3390/ijms21041366
                7072917
                32085571
                061c17bf-be53-4f0b-a15c-4b583086a774
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 December 2019
                : 14 February 2020
                Categories
                Article

                Molecular biology
                fibromyalgia,myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs),human endogenous retrovirus (herv),transposable elements,epigenetics,dna methylation,transfer rna small fragments (tsrnas),interferon (inf),non-hodgkin’s lymphoma

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