Prenatal Diagnosis of Bilateral Ectrodactyly and Radial Agenesis Associated with Trisomy 10 Mosaicism

Ectrodactyly or split hand and foot malformations (SHFMs) are rare malformations of the limbs, characterized by median cles of the hands and feet, syndactyly, and aplasia and/or hypoplasia of the phalanges. ey represent a clinically and genetically heterogeneous disorder, with both sporadic and familial cases. Most of the genomic rearrangements identi�ed to date in some forms of SHFM are autosomal dominant traits, involving various chromosome regions. Bilateral radial ray defects comprise also a large heterogenous group of disorders, including trisomy 18, Fanconi anemia, and thrombocytopenia-absent-radius syndrome, not commonly associated with ectrodactyly. e present paper describes a case of ectrodactyly associated with bilateral radial ray defects, diagnosed in the �rst trimester of pregnancy, in a fetus affected by trisomy 10. Only four cases of sporadic and isolated ectrodactyly, diagnosed by ultrasonography between 14 and 22 weeks' gestation, have been reported. To our knowledge, the present case is the �rst report of mosaic trisomy 10 associated with SHFM and radial aplasia. Trisomy 10 is a rare lethal chromosomal abnormality, most frequently found in abortion products. Only six liveborn mosaic trisomy 10 infants, with severe malformations, dead in early infancy, have been reported. A severe clinical syndrome can be de�ned, comprising ear abnormalities, cle lip/palate, malformations of eyes, heart, and kidneys, and deformity of hands and feet and most oen associated with death neonatally or in early infancy

Contrast-agent-based perfusion MRI code repository and testing framework: ISMRM Open Science Initiative for Perfusion Imaging (OSIPI)

Purpose Software has a substantial impact on quantitative perfusion MRI values. The lack of generally accepted implementations, code sharing and transparent testing reduces reproducibility, hindering the use of perfusion MRI in clinical trials. To address these issues, the ISMRM Open Science Initiative for Perfusion Imaging (OSIPI) aimed to establish a community-led, centralized repository for sharing open-source code for processing contrast-based perfusion imaging, incorporating an open-source testing framework. Methods A repository was established on the OSIPI GitHub website. Python was chosen as the target software language. Calls for code contributions were made to OSIPI members, the ISMRM Perfusion Study Group, and publicly via OSIPI websites. An automated unit-testing framework was implemented to evaluate the output of code contributions, including visual representation of the results. Results The repository hosts 86 implementations of perfusion processing steps contributed by 12 individuals or teams. These cover all core aspects of DCE- and DSC-MRI processing, including multiple implementations of the same functionality. Tests were developed for 52 implementations, covering five analysis steps. For T1 mapping, signal-to-concentration conversion and population AIF functions, different implementations resulted in near-identical output values. For the five pharmacokinetic models tested (Tofts, extended Tofts-Kety, Patlak, two-compartment exchange, and two-compartment uptake), differences in output parameters were observed between contributions. Conclusions The OSIPI DCE-DSC code repository represents a novel community-led model for code sharing and testing. The repository facilitates the re-use of existing code and the benchmarking of new code, promoting enhanced reproducibility in quantitative perfusion imaging

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

Heterozygous variants in ZBTB7A cause a neurodevelopmental disorder associated with symptomatic overgrowth of pharyngeal lymphoid tissue, macrocephaly, and elevated fetal hemoglobin

By clinical whole exome sequencing, we identified 12 individuals with ages 3 to 37 years, including three individuals from the same family, with a consistent phenotype of intellectual disability (ID), macrocephaly, and overgrowth of adenoid tissue. All 12 individuals harbored a rare heterozygous variant in ZBTB7A which encodes the transcription factor Zinc finger and BTB-domain containing protein 7A, known to play a role in lympho- and hematopoiesis. ID was generally mild. Fetal hemoglobin (HbF) fraction was elevated 2.2%–11.2% (reference value  6 months) in four of the five individuals for whom results were available. Ten of twelve individuals had undergone surgery at least once for lymphoid hypertrophy limited to the pharynx. In the most severely affected individual (individual 1), airway obstruction resulted in 17 surgical procedures before the age of 13 years. Sleep apnea was present in 8 of 10 individuals. In the nine unrelated individuals, ZBTB7A variants were novel and de novo. The six frameshift/nonsense and four missense variants were spread throughout the gene. This is the first report of a cohort of individuals with this novel syndromic neurodevelopmental disorder

Acceleration of Seed Extension for BWA-MEM DNA Alignment Using GPUs

DNA aligning is a compute-intensive and time-consuming task required for all further DNA processing. It consists in finding for each DNA string from a sample its location in a reference genome. Usual techniques for short reads (hundreds of bases) involve seed-extension, where a small matching seed is found with quick search through FM-index and then extended on both ends with a custom Smith-Waterman algorithm, giving optimal solution. However this seed-extension takes a tremendous amount of time. This is why we present in this thesis a solution to offload extension on a GPU to be done in a parallel fashion. This is possible thanks to the fact that the DNA reads do not present any kind of relation between each other. We used the Burrows-Wheeler Aligner - Maximal Exact Match (BWA-MEM), a reference program in the field, to which we integrated a GPU-accelerated library for extension, GASAL2. However, BWA-MEM has a left-right dependency on extension starting scores, with the left alignment starting with the seed score, then the right part starting with the previously calculated left score. We designed a solution by starting both extensions with the seed score, we called this method the "seed-only" paradigm. On our test machine featuring 12 hyperthreaded cores and an NVIDIA Tesla K40c, when running with 12 threads, we could observe a raw kernel speed-up of 4.8x ; but if we allow non-blocking calls to let the CPU run the seeding tasks while the GPU computes the extension, we can reach a 16x effective speed-up for the extension. This extension part takes around 27% of the total time but our acceleration introduces a small overhead due to memory preparations and copying, which makes the whole application 1.28x faster, getting close to the theoretical maximum of 1.37x. Additionally, the paradigm shift we operated creates minimal differences in the final main scores on good quality alignments, with a 1.82% difference for our 5.2 million sequences data set. This makes our acceleration with GASAL2 an solid and efficient solution for a single machine