Sirvi Autor "Teder, Hindrek" järgi

Nüüd näidatakse 1 - 6 6

A molecular tool for menstrual cycle phase dating of endometrial samples in endometriosis transcriptome studies
(2019) Saare, Merli; Merli, Triin; Teder, Hindrek; Paluoja, Priit; Palta, Priit; Koel, Mariann; Kirss, Fred; Karro, Helle; Sõritsa, Deniss; Salumets, Andres; Krjutškov, Kaarel; Peters, Maire
Transcriptome profiling of 57 endometrial receptivity genes specifies the menstrual cycle phase of endometrial samples.
Creating basis for introducing non‐invasive prenatal testing in the Estonian public health setting
(John Wiley & Sons, Ltd., 2019-11) Žilina, Olga; Rekker, Kadri; Kaplinski, Lauris; Sauk, Martin; Paluoja, Priit; Teder, Hindrek; Ustav, Eva‐Liina; Tõnisson, Neeme; Reimand, Tiia; Ridnõi, Konstantin; Palta, Priit; Vermeesch, Joris Robert; Krjutškov, Kaarel; Kurg, Ants; Salumet, Andres
Objective The study aimed to validate a whole‐genome sequencing‐based NIPT laboratory method and our recently developed NIPTmer aneuploidy detection software with the potential to integrate the pipeline into prenatal clinical care in Estonia. Method In total, 424 maternal blood samples were included. Analysis pipeline involved cell‐free DNA extraction, library preparation and massively parallel sequencing on Illumina platform. Aneuploidies were determined with NIPTmer software, which is based on counting pre‐defined per‐chromosome sets of unique k‐mers from sequencing raw data. SeqFF was implemented to estimate cell‐free fetal DNA (cffDNA) fraction. Results NIPTmer identified correctly all samples of non‐mosaic trisomy 21 (T21, 15/15), T18 (9/9), T13 (4/4) and monosomy X (4/4) cases, with the 100% sensitivity. However, one mosaic T18 remained undetected. Six false‐positive (FP) results were observed (FP rate of 1.5%, 6/398), including three for T18 (specificity 99.3%) and three for T13 (specificity 99.3%). The level of cffDNA of <4% was estimated in eight samples, including one sample with T13 and T18. Despite low cffDNA level, these two samples were determined as aneuploid. Conclusion We believe that the developed NIPT method can successfully be used as a universal primary screening test in combination with ultrasound scan for the first trimester fetal examination.
Developing computational methods and workflows for targeted and whole-genome sequencing based non-invasive prenatal testing
(2022-05-06) Teder, Hindrek; Palta, Priit, juhendaja; Krjutškov, Kaarel, juhendaja; Salumets, Andres, juhendaja; Tartu Ülikool. Meditsiiniteaduste valdkond
Loote sõeluuring võimaldab avastada lootel esinevaid arenguhäireid ja sagedasemaid kromosoomhaiguseid, nagu näiteks Down’i, Edwards’i ja Patau sündroom. Varajane teave lootel esineva kromosoomhaiguse kohta võimaldab langetada informeeritud otsust raseduse jätkamise osas ning aitab tulevasi vanemaid paremini ette valmistada. Tavapärane loote sõeluuring sisaldab loote ultraheli uuringut ja vereseerumi analüüsi, mille abil tuvastatakse enamik kromosoomhaigusega loodetest. Lõpliku diagnoosi saamiseks suunatakse kõrge riski saanud patsient edasi invasiivsele protseduurile. Eelnimetatud sõeluuringute puuduseks on arvestatav valepositiivsete hulk, mistõttu enamik positiivse testitulemuse saanud patsientidest kannab täiesti tervet loodet. Sõeluuringule järgnev invasiivne protseduur on neil juhtudel ebavajalik, põhjustab rasedatele asjatut stressi ning sellega võib kaasneda suurenenud oht raseduse katkemiseks. Antud doktoritöö keskseks teemaks on mitte-invasiivne sünnieelne testimine (NIPT), mis põhineb ema veres leiduva loote päritolu rakuvaba DNA analüüsil. Võrreldes eelmainitud traditsionaalsete sõeluuringu meetoditega, on NIPT oluliselt sensitiivsem ja spetsiifilisem sagedamini esinevate kromosoomihäirete avastamiseks. Doktoritöö raames arendati välja TAC-seq põhine analüüsi töövoog, mida rakendati 21. kromosoom trisoomia tuvastamiseks. Lisaks töötati välja NIPT analüüsiraamistik, mis kasutab erinevaid masinõppe metoodikaid loote trisoomia määramiseks rakuvaba DNA-st. Niisamuti viidi Eesti rasedate kohordil läbi NIPT metoodika validatsiooni uuring, milles rakendati ülegenoomsel sekveneerimisel põhinevat töövoogu sagedamate loote kromosoomihäirete määramiseks. Üldiselt on nii suunatud kui ka ülegenoomsel NIPT meetoditel muutnud rasedate sõeluuring varasemast veel täpsemaks. Kui suunatud sekveneerimise suureks eeliseks on kulutõhusus, siis ülegenoomne lähenemine tuvastab valimatult kõikvõimalikke geneetilisi aberratsioone üle kogu genoomi.
Evaluation of the possibility to detect fetal chromosome trisomies based on a defined set of single nucleotide polymorphisms for non-invasive prenatal testing
(Tartu Ülikool, 2016) Teder, Hindrek; Tartu Ülikool. Loodus- ja tehnoloogiateaduskond; Tartu Ülikool. Molekulaar- ja rakubioloogia instituut
Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal (cffDNA) from mother’s blood sample has shown to be an accurate and reliable screening tool. The current NIPT protocols are based on targeted or whole genome sequencing, which demand resource-intensive bioinformatical capacity. The complexity of current NIPT technology is trustworthy but the comprehensive adaption of the application is still limited due to the high cost. Mother- and fetus-specific genotypes, according to the nature of cell-free DNA (cfDNA) during pregnancy, were simulated and used in further analysis. Simulations and theoretical calculations demonstrate the characteristic patterns of allelic ratios in case of normal number of chromosomes or trisomy where extra chromosome is inherited from mother or father. Here described analytical approach managed to identify fetal trisomy by comparing the allelic ratios of the risk chromosome with the expected allelic ratios using the t-test and hidden Markov model (HMM) analysis. An average, 3/4 of all highly polymorphic single nucleotide polymorphisms (SNPs) can be used in analysis based on comparison of the allelic ratios. As a result, at least 300 highly polymorphic SNPs over risk and reference chromosomes are needed to detect fetal trisomy using t-test alone. In addition, the HMM analysis can independently detect fetal trisomy and have the ability to distinguish the parental origin of trisomy. Based on the simulated data, the existence and the origin of fetal trisomy is theoretically detectable using a novel and highly quantitative SNP-based approach that is under development by our research group. However, further testing has to be carried out with the real data to confirm the theory.
Geeniekspressiooni uurimine ühe raku tasemel
(Tartu Ülikool, 2013) Teder, Hindrek; Krjutškov, Kaarel, juhendaja; Kurg, Ants, juhendaja; Tartu Ülikool. Loodus- ja tehnoloogiateaduskond; Tartu Ülikool. Molekulaar- ja rakubioloogia instituut
TAC-seq: targeted DNA and RNA sequencing for precise biomarker molecule counting
(2018) Teder, Hindrek; Koel, Mariann; Paluoja, Priit; Jatsenko, Tatjana; Rekker, Kadri; Laisk-Podar, Triin; Kukuškina, Viktorija; Velthut-Meikas, Agne; Fjodorova, Olga; Peters, Maire; Kere, Juha; Salumets, Andres; Palta, Priit; Krjutškov, Kaarel
Targeted next-generation sequencing (NGS) methods have become essential in medical research and diagnostics. In addition to NGS sensitivity and high-throughput capacity, precise biomolecule counting based on unique molecular identifier (UMI) has potential to increase biomolecule detection accuracy. Although UMIs are widely used in basic research its introduction to clinical assays is still in progress. Here, we present a robust and cost-effective TAC-seq (Targeted Allele Counting by sequencing) method that uses UMIs to estimate the original molecule counts of mRNAs, microRNAs, and cell-free DNA. We applied TAC-seq in three different clinical applications and compared the results with standard NGS. RNA samples extracted from human endometrial biopsies were analyzed using previously described 57 mRNA-based receptivity biomarkers and 49 selected microRNAs at different expression levels. Cell-free DNA aneuploidy testing was based on cell line (47,XX, +21) genomic DNA. TAC-seq mRNA profiling showed identical clustering results to transcriptome RNA sequencing, and microRNA detection demonstrated significant reduction in amplification bias, allowing to determine minor expression changes between different samples that remained undetermined by standard NGS. The mimicking experiment for cell-free DNA fetal aneuploidy analysis showed that TAC-seq can be applied to count highly fragmented DNA, detecting significant (p = 7.6 × 10−4) excess of chromosome 21 molecules at 10% fetal fraction level. Based on three proof-of-principle applications we demonstrate that TAC-seq is an accurate and highly potential biomarker profiling method for advanced medical research and diagnostics.