Colib'read on galaxy : a tools suite dedicated to biological information extraction from raw NGS reads

Background: With next-generation sequencing (NGS) technologies, the life sciences face a deluge of raw data. Classical analysis processes for such data often begin with an assembly step, needing large amounts of computing resources, and potentially removing or modifying parts of the biological information contained in the data. Our approach proposes to focus directly on biological questions, by considering raw unassembled NGS data, through a suite of six command-line tools. Findings: Dedicated to 'whole-genome assembly-free' treatments, the Colib'read tools suite uses optimized algorithms for various analyses of NGS datasets, such as variant calling or read set comparisons. Based on the use of a de Bruijn graph and bloom filter, such analyses can be performed in a few hours, using small amounts of memory. Applications using real data demonstrate the good accuracy of these tools compared to classical approaches. To facilitate data analysis and tools dissemination, we developed Galaxy tools and tool shed repositories. Conclusions: With the Colib'read Galaxy tools suite, we enable a broad range of life scientists to analyze raw NGS data. More importantly, our approach allows the maximum biological information to be retained in the data, and uses a very low memory footprint.Peer reviewe

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals —16,036 AD cases and 16,522 controls— in a two-stage analysis. Next to known genes TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Next to these genes, the rare variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential driver genes in AD-GWAS loci. Rare damaging variants in these genes, and in particular loss-of-function variants, have a large effect on AD-risk, and they are enriched in early onset AD cases. The newly identified AD-associated genes provide additional evidence for a major role for APP-processing, Aβ-aggregation, lipid metabolism and microglial function in AD

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease

Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals—16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-β precursor protein processing, amyloid-β aggregation, lipid metabolism and microglial function in AD

Cryopreservation of ex-vitro-grown Rosa chinensis 'Old Blush' buds using droplet-vitrification and encapsulation-dehydration

Axillary buds from greenhouse-grown plants of Rosa chinensis 'Old Blush' were successfully used to establish cryopreservation protocols using both droplet-vitrification and encapsulation-dehydration methods. In droplet vitrification, regrowth occurred after exposure to liquid nitrogen even without pre-culture in the loading solution (LS) before immersion in the plant vitrification solution 2 (PVS2). However, a 20-80 min LS step followed by a short immersion in PVS2 for 3 or 15 min, at 0 A degrees C gave the best regrowth rates (82-86 %). In encapsulation dehydration, the level of dehydration significantly influenced shoot regrowth. The best regrowth rate, 60 %, was obtained at a bead water content of 0.35 g water per g dry weight. These results demonstrate the possibility of using greenhouse plants of rose for cryopreservation by droplet vitrification and encapsulation dehydration

Genotype × Light Quality Interaction on Rose Architecture

Plant shape, and thereby plant architecture, is a major component of the visual quality of ornamental plants. Plant architecture results from growth and branching processes and is dependent on genetic and environmental factors such as light quality. The effects of genotype and light quality and their interaction were evaluated on rose bush architecture. In a climatic growth chamber, three cultivars (Baipome, Knock Out® Radrazz and ‘The Fairy’) with contrasting architecture were exposed to three different light spectra, using white (W), red (R), and far-red (FR) light-emitting diodes (LEDs), i.e., W, WR, and WRFR. The R/FR ratio varied between treatments, ranging from 7.5 for WRFR to 23.2 for WR. Light intensity (224.6 μmol m−2 s−1) was the same for all treatments. Plants were grown up to the order 1 axis flowering stage, and their architecture was digitized at two observation scales—plant and axis. Highly significant genotype and light quality effects were revealed for most of the variables measured. An increase in stem length, in the number of axes and in the number of flowered axes was observed under the FR enriched light, WRFR. However, a strong genotype × light quality interaction, i.e., a genotype-specific response was highlighted. More in-depth eco-physiological and biochemical investigations are needed to better understand rose behavior in response to light quality and thus identify the determinants of the genotype × light quality interaction

Glofitamab Monotherapy in Patients with Non-Hodgkin B-Cell Lymphoma after Failing CAR T-Cell Infusion: Primary Analysis of the Bicar Study, a Phase II Lysa Study

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