Pattern Discovery from Biosequences

In this thesis we have developed novel methods for analyzing biological data, the primary sequences of the DNA and proteins, the microarray based gene expression data, and other functional genomics data. The main contribution is the development of the pattern discovery algorithm SPEXS, accompanied by several practical applications for analyzing real biological problems. For performing these biological studies that integrate different types of biological data we have developed a comprehensive web-based biological data analysis environment Expression Profiler (http://ep.ebi.ac.uk/)

Estonian language technology Anno 2009

Proceedings of the NODALIDA 2009 workshop Nordic Perspectives on the CLARIN Infrastructure of Language Resources. Editors: Rickard Domeij, Kimmo Koskenniemi, Steven Krauwer, Bente Maegaard, Eiríkur Rögnvaldsson and Koenraad de Smedt. NEALT Proceedings Series, Vol. 5 (2009), 21-26. © 2009 The editors and contributors. Published by Northern European Association for Language Technology (NEALT) http://omilia.uio.no/nealt . Electronically published at Tartu University Library (Estonia) http://hdl.handle.net/10062/9207

Kroonilise neeruhaiguse levimus Eesti e-tervise andmete alusel

Taust. Kroonilise neeruhaiguse (KNH) levimus Eestis ei ole teada. Kuna KNH keskmine levimus maailmas on 9,1%, peaks KNH-patsientide arv Eestis olema umbes 118 300. Samas on 2017. aasta üleilmse aruande kohaselt KNH patsientide arv Eestis 258 859, mis on tõenäoliselt ülehinnatud.Eesti e-tervis on alustalaks tervishoiuandmete registreerimisele ja kogumisele. Samas on andmete analüüs tihti tüsilik, sest väljunddokumendid on erinevas formaadis, ja see raskendab oluliselt analüüsi. Lisaks pole haiguslugudes sageli märgitud diagnoosikoode ja/või KNH raskuskategooriat.Eesmärk. Töö eesmärk oli selgitada KNH levimust ja käsitlust Eestis, hinnates e-tervise infosüsteemi andmete põhjal retrospektiivselt täiskasvanud KNH-patsientide hulka ja jaotust vastavalt KNH riskiprofiilile, kasutades esimest korda ka tehisintellekti abi.Meetodid. Uuringu alusandmestiku moodustas Eesti elanikkonna 10% juhuvalimi raviarvete, digiretsepti ja tervise infosüsteemi andmete (e-tervise andmed) ühendväljavõte (sh eriarstiabi, perearstiabi, ostetud ravimid, laboratoorsed andmed). Uuringupopulatsioon määratleti kui kõik vähemalt 18aastased patsiendid, kellel oli ajavahemikul 2016–2019 diagnoositud vähemalt üks haigus, mis on KNH riskitegur, ja/ või kellel oli 2019. aasta jooksul vähemalt ühel korral registreeritud hinnangulise glomerulaarfiltratsiooni kiiruse (eGFR) ja/või uriinis albumiini-kreatiniini suhte (U-Alb/U-Crea, UACR) väärtus. Analüüsiti ka patsientide väljaostetud ravimeid, haiglaravi ja/või erakorralise meditsiini osakonna (EMO) juhtude arvu. Erinevas formaadis väljunddokumentide analüüsimiseks kasutati tehisintellekti abi, mille käigus transformeeriti epikriisi tekstifailis olev info analüüsis kasutatavale kujule.Tulemused. E-tervise andmete alusel tuvastati 5%-l elanikkonnast juba olemasolev KNH diagnoos ja lisaks 2,4%-l potentsiaalne KNH raskusastmega G3–G5. Nende andmete kohaselt võib Eestis kokku olla 83 710 KNH-patsienti ja KNH levimus täiskasvanud elanikkonnas on 7,4%. eGFR-i väärtused olid uuringus kättesaadavad 52%-l riskipatsientidest, UARC väärtused aga vaid 12%-l. Hulgihaigestumise hindamisel leiti, et KNH-patsientidel esineb kaasnevalt kõige sagedamini hüpertensioon (79%), südame-veresoonkonnahaigus (SVH) (63%) ja diabeet (28%). Ligi pooled KNH-patsientidest olid ühe aasta jooksul hospitaliseeritud või pöördunud EMOsse. Selle peamiseks põhjuseks oli olnud SVH (11%). KNH diagnoosiga patsiendid eristuvad KNH riskirühma kuuluvatest patsientidest (diabeet, hüpertensioon, SVH) suurema hospitaliseerimismäära ja erakorralise abi vajaduse poolest.Järeldused. KNH levimus Eestis täiskasvanud elanikkonnas on e-tervise andmetel 7,4%. Hoolimata riikliku KNH ravijuhendi olemasolust ning KNH sõeluuringu süsteemist diabeedi ja hüpertensiooni korral esineb lünki patsientide skriinimises, neeruhaiguse progresseerumise riski hindamises ja patsientide tõenduspõhises ravis. KNH tekkeriski ja progresseerumise tuvastamiseks ja asjakohase ravi tagamiseks on KNH riskirühmade seas vaja järgida ravijuhendit UARC väärtuse määramisel ning täpsustada alati ka KNH raskusaste koos albuminuuria kategooriaga. KNH-patsientide haiguskoormus on suur ning nende patsientide käsitlus nõuab tihedat koostööd esmatasandi tervishoiu ja eriarstide vahel. Seetõttu on KNH progresseerumise ennetamiseks tarvis enam ressursse

Gene Expression-Based Approaches in Differentiation of Metastases and Second Primary Tumour

A 64-year-old male patient was diagnosed with 3 consecutive non-small cell lung carcinomas (NSCLC). In the current study, we applied whole-genome gene expression analysis to control, primary and locally recurrent cancer, and supposed metastasis samples of a single patient. According to our knowledge, there are no published papers describing the gene expression profiles of a single patient's squamous cell lung cancers. As the histology and differentiation grade of the primary cancer and the supposed metastasis differed minimally, but local recurrence was poorly differentiated, molecular profiling of the samples was carried out in order to confirm or reject the hypothesis of second primary cancer. Principal component analysis of the gene expression data revealed distinction of the local recurrence. Gene ontology analysis showed no molecular characteristics of metastasis in the supposed metastasis. Gene expression analysis is valuable and can be supportive in decision-making of diagnostically complicated cancer cases

Personaalmeditsiini keskuse loomisest Eestis

Eesti Arst 2023; 102(2):76–7

Comprehensive transcriptome analysis of mouse embryonic stem cell adipogenesis unravels new processes of adipocyte development

International audienceBACKGROUND: The current epidemic of obesity has caused a surge of interest in the study of adipose tissue formation. While major progress has been made in defining the molecular networks that control adipocyte terminal differentiation, the early steps of adipocyte development and the embryonic origin of this lineage remain largely unknown. RESULTS: Here we performed genome-wide analysis of gene expression during adipogenesis of mouse embryonic stem cells (ESCs). We then pursued comprehensive bioinformatic analyses, including de novo functional annotation and curation of the generated data within the context of biological pathways, to uncover novel biological functions associated with the early steps of adipocyte development. By combining in-depth gene regulation studies and in silico analysis of transcription factor binding site enrichment, we also provide insights into the transcriptional networks that might govern these early steps. CONCLUSIONS: This study supports several biological findings: firstly, adipocyte development in mouse ESCs is coupled to blood vessel morphogenesis and neural development, just as it is during mouse development. Secondly, the early steps of adipocyte formation involve major changes in signaling and transcriptional networks. A large proportion of the transcription factors that we uncovered in mouse ESCs are also expressed in the mouse embryonic mesenchyme and in adipose tissues, demonstrating the power of our approach to probe for genes associated with early developmental processes on a genome-wide scale. Finally, we reveal a plethora of novel candidate genes for adipocyte development and present a unique resource that can be further explored in functional assays

Autoantibody Repertoire in APECED Patients Targets Two Distinct Subgroups of Protiens

High titer autoantibodies produced by B lymphocytes are clinically important features of many common autoimmune diseases. APECED patients with deficient autoimmune regulator (AIRE) gene collectively display a broad repertoire of high titer autoantibodies, including some which are pathognomonic for major autoimmune diseases. AIRE deficiency severely reduces thymic expression of gene-products ordinarily restricted to discrete peripheral tissues, and developing T cells reactive to those gene-products are not inactivated during their development. However, the extent of the autoantibody repertoire in APECED and its relation to thymic expression of self-antigens are unclear. We here undertook a broad protein array approach to assess autoantibody repertoire in APECED patients. Our results show that in addition to shared autoantigen reactivities, APECED patients display high inter-individual variation in their autoantigen profiles, which collectively are enriched in evolutionarily conserved, cytosolic and nuclear phosphoproteins. The APECED autoantigens have two major origins; proteins expressed in thymic medullary epithelial cells and proteins expressed in lymphoid cells. These findings support the hypothesis that specific protein properties strongly contribute to the etiology of B cell autoimmunity.Peer reviewe

Prostaglandin D2 Receptor DP1 Antibodies Predict Vaccine-induced and Spontaneous Narcolepsy Type 1 : Large-scale Study of Antibody Profiling

AbstractBackground Neuropathological findings support an autoimmune etiology as an underlying factor for loss of orexin-producing neurons in spontaneous narcolepsy type 1 (narcolepsy with cataplexy; sNT1) as well as in Pandemrix influenza vaccine-induced narcolepsy type 1 (Pdmx-NT1). The precise molecular target or antigens for the immune response have, however, remained elusive. Methods Here we have performed a comprehensive antigenic repertoire analysis of sera using the next-generation phage display method - mimotope variation analysis (MVA). Samples from 64 children and adolescents were analyzed: 10 with Pdmx-NT1, 6 with sNT1, 16 Pandemrix-vaccinated, 16 H1N1 infected, and 16 unvaccinated healthy individuals. The diagnosis of NT1 was defined by the American Academy of Sleep Medicine international criteria of sleep disorders v3. Findings Our data showed that although the immunoprofiles toward vaccination were generally similar in study groups, there were also striking differences in immunoprofiles between sNT1 and Pdmx-NT1 groups as compared with controls. Prominent immune response was observed to a peptide epitope derived from prostaglandin D2 receptor (DP1), as well as peptides homologous to B cell lymphoma 6 protein. Further validation confirmed that these can act as true antigenic targets in discriminating NT1 diseased along with a novel epitope of hemagglutinin of H1N1 to delineate exposure to H1N1. Interpretation We propose that DP1 is a novel molecular target of autoimmune response and presents a potential diagnostic biomarker for NT1. DP1 is involved in the regulation of non-rapid eye movement (NREM) sleep and thus alterations in its functions could contribute to the disturbed sleep regulation in NT1 that warrants further studies. Together our results also show that MVA is a helpful method for finding novel peptide antigens to classify human autoimmune diseases, possibly facilitating the design of better therapies.Peer reviewe