--- _id: '10702' abstract: - lang: eng text: 'Background: Blood-based markers of cognitive functioning might provide an accessible way to track neurodegeneration years prior to clinical manifestation of cognitive impairment and dementia. Results: Using blood-based epigenome-wide analyses of general cognitive function, we show that individual differences in DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic score, in two external cohorts. It also associates with circulating levels of neurology- and inflammation-related proteins, global brain imaging metrics, and regional cortical volumes. Conclusions: As sample sizes increase, the ability to assess cognitive function from DNAm data may be informative in settings where cognitive testing is unreliable or unavailable.' acknowledgement: 'GS received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award STratifying Resilience and Depression Longitudinally (STRADL; Reference 104036/Z/14/Z). The DNA methylation data assayed for Generation Scotland was partially funded by a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Ref: 27404; awardee: Dr David M Howard) and by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh (Awardee: Dr Heather C Whalley). LBC1936 MRI brain imaging was supported by Medical Research Council (MRC) grants [G0701120], [G1001245], [MR/M013111/1] and [MR/R024065/1]. Magnetic resonance image acquisition and analyses were conducted at the Brain Research Imaging Centre, Neuroimaging Sciences, University of Edinburgh (www.bric.ed.ac.uk) which is part of SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence) collaboration (www.sinapse.ac.uk) funded by the Scottish Funding Council and the Chief Scientist Office. This work was supported by the European Union Horizon 2020 (PHC.03.15, project No 666881), SVDs@Target, the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease [ref no. 16 CVD 05]. We thank the LBC1936 participants and team members who contributed to these studies. The LBC1936 is supported by Age UK (Disconnected Mind project, which supports S.E.H.), the Medical Research Council (G0701120, G1001245, MR/M013111/1, MR/R024065/1) and the University of Edinburgh. Methylation typing of LBC1936 was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. Genotyping was funded by the Biotechnology and Biological Sciences Research Council (BB/F019394/1). Proteomic analyses in LBC1936 were supported by the Age UK grant and NIH Grants R01AG054628 and R01AG05462802S1. M.V.H. is funded by the Row Fogo Charitable Trust (Grant no. BROD.FID3668413). J.M.W is supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimers Society and Alzheimers Research UK. R.F.H., E.L.S.C and D.A.G. are supported by funding from the Wellcome Trust 4 year PhD in Translational Neuroscience: training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z]. E.M.T.D. was supported by the National Institutes of Health (NIH) grants R01AG054628, R01MH120219, R01HD083613, P2CHD042849 and P30AG066614. S.R.C. was also supported by a National Institutes of Health (NIH) research grant R01AG054628 and is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 221890/Z/20/Z). D.L.Mc.C. and R.E.M. are supported by Alzheimers Research UK major project grant ARUK/PG2017B/10. R.E.M. is supported by Alzheimer’s Society major project grant AS-PG-19b-010. This research was funded in whole, or in part, by Wellcome [104036/Z/14/Z and 108890/Z/15/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.' article_number: '26' article_processing_charge: No article_type: original author: - first_name: Daniel L. full_name: McCartney, Daniel L. last_name: McCartney - first_name: Robert F. full_name: Hillary, Robert F. last_name: Hillary - first_name: Eleanor L.S. full_name: Conole, Eleanor L.S. last_name: Conole - first_name: Daniel Trejo full_name: Banos, Daniel Trejo last_name: Banos - first_name: Danni A. full_name: Gadd, Danni A. last_name: Gadd - first_name: Rosie M. full_name: Walker, Rosie M. last_name: Walker - first_name: Cliff full_name: Nangle, Cliff last_name: Nangle - first_name: Robin full_name: Flaig, Robin last_name: Flaig - first_name: Archie full_name: Campbell, Archie last_name: Campbell - first_name: Alison D. full_name: Murray, Alison D. last_name: Murray - first_name: Susana Muñoz full_name: Maniega, Susana Muñoz last_name: Maniega - first_name: María Del C. full_name: Valdés-Hernández, María Del C. last_name: Valdés-Hernández - first_name: Mathew A. full_name: Harris, Mathew A. last_name: Harris - first_name: Mark E. full_name: Bastin, Mark E. last_name: Bastin - first_name: Joanna M. full_name: Wardlaw, Joanna M. last_name: Wardlaw - first_name: Sarah E. full_name: Harris, Sarah E. last_name: Harris - first_name: David J. full_name: Porteous, David J. last_name: Porteous - first_name: Elliot M. full_name: Tucker-Drob, Elliot M. last_name: Tucker-Drob - first_name: Andrew M. full_name: McIntosh, Andrew M. last_name: McIntosh - first_name: Kathryn L. full_name: Evans, Kathryn L. last_name: Evans - first_name: Ian J. full_name: Deary, Ian J. last_name: Deary - first_name: Simon R. full_name: Cox, Simon R. last_name: Cox - first_name: Matthew Richard full_name: Robinson, Matthew Richard id: E5D42276-F5DA-11E9-8E24-6303E6697425 last_name: Robinson orcid: 0000-0001-8982-8813 - first_name: Riccardo E. full_name: Marioni, Riccardo E. last_name: Marioni citation: ama: McCartney DL, Hillary RF, Conole ELS, et al. Blood-based epigenome-wide analyses of cognitive abilities. Genome Biology. 2022;23(1). doi:10.1186/s13059-021-02596-5 apa: McCartney, D. L., Hillary, R. F., Conole, E. L. S., Banos, D. T., Gadd, D. A., Walker, R. M., … Marioni, R. E. (2022). Blood-based epigenome-wide analyses of cognitive abilities. Genome Biology. Springer Nature. https://doi.org/10.1186/s13059-021-02596-5 chicago: McCartney, Daniel L., Robert F. Hillary, Eleanor L.S. Conole, Daniel Trejo Banos, Danni A. Gadd, Rosie M. Walker, Cliff Nangle, et al. “Blood-Based Epigenome-Wide Analyses of Cognitive Abilities.” Genome Biology. Springer Nature, 2022. https://doi.org/10.1186/s13059-021-02596-5. ieee: D. L. McCartney et al., “Blood-based epigenome-wide analyses of cognitive abilities,” Genome Biology, vol. 23, no. 1. Springer Nature, 2022. ista: McCartney DL, Hillary RF, Conole ELS, Banos DT, Gadd DA, Walker RM, Nangle C, Flaig R, Campbell A, Murray AD, Maniega SM, Valdés-Hernández MDC, Harris MA, Bastin ME, Wardlaw JM, Harris SE, Porteous DJ, Tucker-Drob EM, McIntosh AM, Evans KL, Deary IJ, Cox SR, Robinson MR, Marioni RE. 2022. Blood-based epigenome-wide analyses of cognitive abilities. Genome Biology. 23(1), 26. mla: McCartney, Daniel L., et al. “Blood-Based Epigenome-Wide Analyses of Cognitive Abilities.” Genome Biology, vol. 23, no. 1, 26, Springer Nature, 2022, doi:10.1186/s13059-021-02596-5. short: D.L. McCartney, R.F. Hillary, E.L.S. Conole, D.T. Banos, D.A. Gadd, R.M. Walker, C. Nangle, R. Flaig, A. Campbell, A.D. Murray, S.M. Maniega, M.D.C. Valdés-Hernández, M.A. Harris, M.E. Bastin, J.M. Wardlaw, S.E. Harris, D.J. Porteous, E.M. Tucker-Drob, A.M. McIntosh, K.L. Evans, I.J. Deary, S.R. Cox, M.R. Robinson, R.E. Marioni, Genome Biology 23 (2022). date_created: 2022-01-30T23:01:33Z date_published: 2022-01-17T00:00:00Z date_updated: 2023-08-02T14:05:13Z day: '17' ddc: - '570' department: - _id: MaRo doi: 10.1186/s13059-021-02596-5 external_id: isi: - '000744358300002' file: - access_level: open_access checksum: 34f10bb2b0594189dcac24d13b691d52 content_type: application/pdf creator: cchlebak date_created: 2022-01-31T13:16:05Z date_updated: 2022-01-31T13:16:05Z file_id: '10708' file_name: 2022_GenomeBio_McCartney.pdf file_size: 1540606 relation: main_file success: 1 file_date_updated: 2022-01-31T13:16:05Z has_accepted_license: '1' intvolume: ' 23' isi: 1 issue: '1' language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 9B8D11D6-BA93-11EA-9121-9846C619BF3A grant_number: PCEGP3_181181 name: Improving estimation and prediction of common complex disease risk publication: Genome Biology publication_identifier: eissn: - 1474-760X issn: - 1474-7596 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: earlier_version url: https://doi.org/10.1101/2021.05.24.21257698 record: - id: '13072' relation: research_data status: public scopus_import: '1' status: public title: Blood-based epigenome-wide analyses of cognitive abilities tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2022' ... --- _id: '11587' abstract: - lang: eng text: "Background: Accurate and comprehensive annotation of transcript sequences is essential for transcript quantification and differential gene and transcript expression analysis. Single-molecule long-read sequencing technologies provide improved integrity of transcript structures including alternative splicing, and transcription start and polyadenylation sites. However, accuracy is significantly affected by sequencing errors, mRNA degradation, or incomplete cDNA synthesis.\r\nResults: We present a new and comprehensive Arabidopsis thaliana Reference Transcript Dataset 3 (AtRTD3). AtRTD3 contains over 169,000 transcripts—twice that of the best current Arabidopsis transcriptome and including over 1500 novel genes. Seventy-eight percent of transcripts are from Iso-seq with accurately defined splice junctions and transcription start and end sites. We develop novel methods to determine splice junctions and transcription start and end sites accurately. Mismatch profiles around splice junctions provide a powerful feature to distinguish correct splice junctions and remove false splice junctions. Stratified approaches identify high-confidence transcription start and end sites and remove fragmentary transcripts due to degradation. AtRTD3 is a major improvement over existing transcriptomes as demonstrated by analysis of an Arabidopsis cold response RNA-seq time-series. AtRTD3 provides higher resolution of transcript expression profiling and identifies cold-induced differential transcription start and polyadenylation site usage.\r\nConclusions: AtRTD3 is the most comprehensive Arabidopsis transcriptome currently. It improves the precision of differential gene and transcript expression, differential alternative splicing, and transcription start/end site usage analysis from RNA-seq data. The novel methods for identifying accurate splice junctions and transcription start/end sites are widely applicable and will improve single-molecule sequencing analysis from any species." acknowledgement: "This work was jointly supported by funding from the Biotechnology and Biological Sciences Research Council (BBSRC) BB/P009751/1 to JB; BB/R014582/1 to RW and RZ; BB/S020160/1 to RZ; BB/S004610/1 (16 ERA-CAPS BARN) to RW; the Scottish Government Rural and Environment Science and Analytical Services division (RESAS) [to RZ, RW, and JB]; the\r\nNational Science Foundation (MCB-2014408) and the National Institute of Health (NIH) (GM-114297) to E.H.; S. H. was supported by funding to K.D. from the University of York; the Austrian Science Fund (FWF) SFB F43 to AB and MJ and [P26333] to MK; The French Agence Nationale de la Recherche grant ANR-16-CE12-0032 to MC; the Japan Science and\r\nTechnology Agency (JST), the Core Research for Evolutionary Science and Technology (CREST; Grant Number JPMJCR13B4) to M.S.; the National Science Foundation (Grant No. DBI1949036 to A.b.H and A.S.N.R, and Grant No. MCB 2014542 to E.H. and A.S.N.R.); and the DOE Office of Science, Office of Biological and Environmental Research (Grant\r\nNo. DE-SC0010733) to A.S.N.R and A.b.H.; the Deutsche Forschungsgemeinschaft (DFG) STA653/14-1 and STA653/15-1 to DS; the National Science Foundation grant (IOS-154173) to Q.Q.L.; the German Research Foundation (DFG) WA2167/8-1 to AW and SFB1101/C03 to AW and TWK; the Research Grants Council (RGC) of Hong Kong (GRF 12103020) to LX. NSF grant IOS-1849708 and NSF EPSCoR grant 1826836 to RS; the Academia Sinica to S.-L. T." article_number: '149' article_processing_charge: No article_type: original author: - first_name: Runxuan full_name: Zhang, Runxuan last_name: Zhang - first_name: Richard full_name: Kuo, Richard last_name: Kuo - first_name: Max full_name: Coulter, Max last_name: Coulter - first_name: Cristiane P.G. full_name: Calixto, Cristiane P.G. last_name: Calixto - first_name: Juan Carlos full_name: Entizne, Juan Carlos last_name: Entizne - first_name: Wenbin full_name: Guo, Wenbin last_name: Guo - first_name: Yamile full_name: Marquez, Yamile last_name: Marquez - first_name: Linda full_name: Milne, Linda last_name: Milne - first_name: Stefan full_name: Riegler, Stefan id: FF6018E0-D806-11E9-8E43-0B14E6697425 last_name: Riegler orcid: 0000-0003-3413-1343 - first_name: Akihiro full_name: Matsui, Akihiro last_name: Matsui - first_name: Maho full_name: Tanaka, Maho last_name: Tanaka - first_name: Sarah full_name: Harvey, Sarah last_name: Harvey - first_name: Yubang full_name: Gao, Yubang last_name: Gao - first_name: Theresa full_name: Wießner-Kroh, Theresa last_name: Wießner-Kroh - first_name: Alejandro full_name: Paniagua, Alejandro last_name: Paniagua - first_name: Martin full_name: Crespi, Martin last_name: Crespi - first_name: Katherine full_name: Denby, Katherine last_name: Denby - first_name: Asa Ben full_name: Hur, Asa Ben last_name: Hur - first_name: Enamul full_name: Huq, Enamul last_name: Huq - first_name: Michael full_name: Jantsch, Michael last_name: Jantsch - first_name: Artur full_name: Jarmolowski, Artur last_name: Jarmolowski - first_name: Tino full_name: Koester, Tino last_name: Koester - first_name: Sascha full_name: Laubinger, Sascha last_name: Laubinger - first_name: Qingshun Quinn full_name: Li, Qingshun Quinn last_name: Li - first_name: Lianfeng full_name: Gu, Lianfeng last_name: Gu - first_name: Motoaki full_name: Seki, Motoaki last_name: Seki - first_name: Dorothee full_name: Staiger, Dorothee last_name: Staiger - first_name: Ramanjulu full_name: Sunkar, Ramanjulu last_name: Sunkar - first_name: Zofia full_name: Szweykowska-Kulinska, Zofia last_name: Szweykowska-Kulinska - first_name: Shih Long full_name: Tu, Shih Long last_name: Tu - first_name: Andreas full_name: Wachter, Andreas last_name: Wachter - first_name: Robbie full_name: Waugh, Robbie last_name: Waugh - first_name: Liming full_name: Xiong, Liming last_name: Xiong - first_name: Xiao Ning full_name: Zhang, Xiao Ning last_name: Zhang - first_name: Ana full_name: Conesa, Ana last_name: Conesa - first_name: Anireddy S.N. full_name: Reddy, Anireddy S.N. last_name: Reddy - first_name: Andrea full_name: Barta, Andrea last_name: Barta - first_name: Maria full_name: Kalyna, Maria last_name: Kalyna - first_name: John W.S. full_name: Brown, John W.S. last_name: Brown citation: ama: Zhang R, Kuo R, Coulter M, et al. A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis. Genome Biology. 2022;23. doi:10.1186/s13059-022-02711-0 apa: Zhang, R., Kuo, R., Coulter, M., Calixto, C. P. G., Entizne, J. C., Guo, W., … Brown, J. W. S. (2022). A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis. Genome Biology. BioMed Central. https://doi.org/10.1186/s13059-022-02711-0 chicago: Zhang, Runxuan, Richard Kuo, Max Coulter, Cristiane P.G. Calixto, Juan Carlos Entizne, Wenbin Guo, Yamile Marquez, et al. “A High-Resolution Single-Molecule Sequencing-Based Arabidopsis Transcriptome Using Novel Methods of Iso-Seq Analysis.” Genome Biology. BioMed Central, 2022. https://doi.org/10.1186/s13059-022-02711-0. ieee: R. Zhang et al., “A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis,” Genome Biology, vol. 23. BioMed Central, 2022. ista: Zhang R, Kuo R, Coulter M, Calixto CPG, Entizne JC, Guo W, Marquez Y, Milne L, Riegler S, Matsui A, Tanaka M, Harvey S, Gao Y, Wießner-Kroh T, Paniagua A, Crespi M, Denby K, Hur AB, Huq E, Jantsch M, Jarmolowski A, Koester T, Laubinger S, Li QQ, Gu L, Seki M, Staiger D, Sunkar R, Szweykowska-Kulinska Z, Tu SL, Wachter A, Waugh R, Xiong L, Zhang XN, Conesa A, Reddy ASN, Barta A, Kalyna M, Brown JWS. 2022. A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis. Genome Biology. 23, 149. mla: Zhang, Runxuan, et al. “A High-Resolution Single-Molecule Sequencing-Based Arabidopsis Transcriptome Using Novel Methods of Iso-Seq Analysis.” Genome Biology, vol. 23, 149, BioMed Central, 2022, doi:10.1186/s13059-022-02711-0. short: R. Zhang, R. Kuo, M. Coulter, C.P.G. Calixto, J.C. Entizne, W. Guo, Y. Marquez, L. Milne, S. Riegler, A. Matsui, M. Tanaka, S. Harvey, Y. Gao, T. Wießner-Kroh, A. Paniagua, M. Crespi, K. Denby, A.B. Hur, E. Huq, M. Jantsch, A. Jarmolowski, T. Koester, S. Laubinger, Q.Q. Li, L. Gu, M. Seki, D. Staiger, R. Sunkar, Z. Szweykowska-Kulinska, S.L. Tu, A. Wachter, R. Waugh, L. Xiong, X.N. Zhang, A. Conesa, A.S.N. Reddy, A. Barta, M. Kalyna, J.W.S. Brown, Genome Biology 23 (2022). date_created: 2022-07-17T22:01:53Z date_published: 2022-07-07T00:00:00Z date_updated: 2023-08-03T12:04:18Z day: '07' ddc: - '570' department: - _id: FyKo doi: 10.1186/s13059-022-02711-0 external_id: isi: - '000821915500002' file: - access_level: open_access checksum: 2c30ef84151d257a6b835b4e069b70ac content_type: application/pdf creator: dernst date_created: 2022-07-18T08:15:24Z date_updated: 2022-07-18T08:15:24Z file_id: '11597' file_name: 2022_GenomeBiology_Zhang.pdf file_size: 3146207 relation: main_file success: 1 file_date_updated: 2022-07-18T08:15:24Z has_accepted_license: '1' intvolume: ' 23' isi: 1 language: - iso: eng month: '07' oa: 1 oa_version: Published Version publication: Genome Biology publication_identifier: eissn: - 1474-760X publication_status: published publisher: BioMed Central quality_controlled: '1' scopus_import: '1' status: public title: A high-resolution single-molecule sequencing-based Arabidopsis transcriptome using novel methods of Iso-seq analysis tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 23 year: '2022' ...