| 1. |
- Miller, David T., et al.
(författare)
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Consensus Statement : Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies
- 2010
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 86:5, s. 749-764
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal microarray (CMA) is increasingly utilized for genetic testing of individuals with unexplained developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), or multiple congenital anomalies (MCA). Performing CMA and G-banded karyotyping on every patient substantially increases the total cost of genetic testing. The International Standard Cytogenomic Array (ISCA) Consortium held two international workshops and conducted a literature review of 33 studies, including 21,698 patients tested by CMA. We provide an evidence-based summary of clinical cytogenetic testing comparing CMA to G-banded karyotyping with respect to technical advantages and limitations, diagnostic yield for various types of chromosomal aberrations, and issues that affect test interpretation. CMA offers a much higher diagnostic yield (15%-20%) for genetic testing of individuals with unexplained DD/ID, ASD, or MCA than a G-banded karyotype (similar to 3%, excluding Down syndrome and other recognizable chromosomal syndromes), primarily because of its higher sensitivity for submicroscopic deletions and duplications. Truly balanced rearrangements and low-level mosaicism are generally not detectable by arrays, but these are relatively infrequent causes of abnormal phenotypes in this population (<1%). Available evidence strongly supports the use of CMA in place of G-banded karyotyping as the first-tier cytogenetic diagnostic test for patients with DD/ID, ASD, or MCA. G-banded karyotype analysis should be reserved for patients with obvious chromosomal syndromes (e.g., Down syndrome), a family history of chromosomal rearrangement, or a history of multiple miscarriages.
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| 2. |
- Paluoja, P, et al.
(författare)
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Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples
- 2021
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Ingår i: PLoS computational biology. - : Public Library of Science (PLoS). - 1553-7358. ; 17:12, s. e1009684-
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no prior comprehensive, head-to-head accuracy comparison of the various tools has been published. Here, we compared the outcome accuracies obtained for clinically validated samples with five commonly used computational NIPT aneuploidy analysis tools (WisecondorX, NIPTeR, NIPTmer, RAPIDR, and GIPseq) across various sequencing depths (coverage) and fetal DNA fractions. The sample set included cases of fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). We determined that all of the compared tools were considerably affected by lower sequencing depths, such that increasing proportions of undetected trisomy cases (false negatives) were observed as the sequencing depth decreased. We summarised our benchmarking results and highlighted the advantages and disadvantages of each computational NIPT software. To conclude, trisomy detection for lower coverage NIPT samples (e.g. 2.5M reads per sample) is technically possible but can, with some NIPT tools, produce troubling rates of inaccurate trisomy detection, especially in low-FF samples.
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| 3. |
- Sauk, M, et al.
(författare)
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NIPTmer: rapid k-mer-based software package for detection of fetal aneuploidies
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 5616-
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Tidskriftsartikel (refereegranskat)abstract
- Non-invasive prenatal testing (NIPT) is a recent and rapidly evolving method for detecting genetic lesions, such as aneuploidies, of a fetus. However, there is a need for faster and cheaper laboratory and analysis methods to make NIPT more widely accessible. We have developed a novel software package for detection of fetal aneuploidies from next-generation low-coverage whole genome sequencing data. Our tool – NIPTmer – is based on counting pre-defined per-chromosome sets of unique k-mers from raw sequencing data, and applying linear regression model on the counts. Additionally, the filtering process used for k-mer list creation allows one to take into account the genetic variance in a specific sample, thus reducing the source of uncertainty. The processing time of one sample is less than 10 CPU-minutes on a high-end workstation. NIPTmer was validated on a cohort of 583 NIPT samples and it correctly predicted 37 non-mosaic fetal aneuploidies. NIPTmer has the potential to reduce significantly the time and complexity of NIPT post-sequencing analysis compared to mapping-based methods. For non-commercial users the software package is freely available at http://bioinfo.ut.ee/NIPTMer/.
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| 6. |
- Breitfeld, H. T., et al.
(författare)
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The onshore West Baram Delta deposits: Provenance and drainage in the Middle Miocene to Pliocene in NW Borneo and comparison to the Champion Delta
- 2023
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Ingår i: Marine and Petroleum Geology. - 0264-8172. ; 158
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Tidskriftsartikel (refereegranskat)abstract
- The Baram Delta province in NW Borneo forms a major hydrocarbon reservoir offshore northern Sarawak and Brunei. The delta sequence is thereby subdivided into the West Baram delta to the south and the Champion delta to the north. Onshore are the remains of the Neogene delta deposits exposed and provide the possibility to study the equivalent offshore successions in outcrop. This study focuses on the Neogene West Baram delta successions which were studied for sedimentological facies and provenance characteristics. The successions consist of the Lambir, Miri, Tukau, and the enigmatic southern Lambir/Belait-Sarawak formations. Deposition took place in various mixed-energy delta environments between the Langhian and early Pliocene. The sediments are all quartzrich and heavy minerals are dominated by ultra-stable zircon, rutile and tourmaline. Dominant detrital zircon age clusters are in the Early Cretaceous and Permian-Triassic. Based on light mineral petrography, heavy mineral assemblages, and detrital zircon U-Pb geochronology, all formations are interpreted as derived from multirecycled sources, likely the underlying Paleogene Rajang Group turbidites and the Oligocene to Lower Miocene Nyalau-Tatau delta deposits. Additionally, literature data of the Champion Delta and one sample from Labuan analysed for provenance in this study are used to demonstrate that the Champion Delta can be distinguished from the West Baram Delta by having higher chrome spinel and garnet contents and slightly different detrital zircon age populations. The Champion Delta deposits are interpreted as sourced by recycling of the Crocker Formation and older turbidites (e.g., Sapulut Formation) with potentially input from ultra-mafic basement rocks of Sabah.
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| 9. |
- Vermeesch, P., et al.
(författare)
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A genetic classification of the tholeiitic and calc-alkaline magma series
- 2021
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Ingår i: Geochemical Perspectives Letters. - : European Association of Geochemistry. - 2410-339X .- 2410-3403. ; 19, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- The concept of the ‘magma series’ and the distinction between alkaline, calc-alkaline and tholeiitic trends has been a cornerstone in igneous petrology since the early 20th century, and encodes fundamental information about the redox state of divergent and convergent plate tectonic settings. We show that the ‘Bowen and Fenner trends’ that characterise the calc-alkaline and tholeiitic types of magmatic environments can be approximated by a simple log ratio model based on three coupled exponential decay functions, for A = Na2O + K2O, F = FeOT and M = MgO, respectively. We use this simple natural law to define a ‘Bowen-Fenner Index’ to quantify the degree to which an igneous rock belongs to either magma series. Applying our model to a data compilation of igneous rocks from Iceland and the Cascade Mountains effectively separates these into tholeiitic and calc-alkaline trends. However the simple model fails to capture the distinct dog-leg that characterises the tholeiitic log ratio evolution, which can be attributed to the switch from ferrous to ferric iron-bearing minerals. Parameterising this switch in a two stage magma evolution model results in a more accurate fit to the Icelandic data. The same two stage model can also be fitted in A–T–M space, where ‘T’ stands for TiO2. This produces a new way to identify calc-alkaline and tholeiitic rocks that does not require the conversion of FeO and Fe2O3 to FeOT. Our results demonstrate that log ratio analysis provides a natural way to parameterise physical processes that give rise to these magma series.
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