Modern organizations often consist of teams in which some people are collocated and some are remote. These teams are in-between being entirely virtual to entirely face-to-face and are referred to as ...partially distributed teams. Partially distributed teams function and operate in two different media environments, varying in availability of communication channels. These media environments may encourage different communication patterns, widening a gap produced by distance. In two laboratory studies we demonstrate that different electronic communication norms (ECNs) emerge among members of the same team based on their media environments. Most of the norms regarding use of electronic communication persisted even when media environment was changed. This difference in ECNs might serve as an additional faultline, causing an additional rift within distributed teams.
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CEKLJ, FFLJ, NUK, ODKLJ, PEFLJ
Von Recklinghausen neurofibromatosis is a common autosomal dominant genetic disorder characterized by benign and malignant tumors of neural crest origin. Significant progress in understanding the ...pathophysiology of this disease has occurred in recent years, largely aided by the development of relevant animal models. Von Recklinghausen neurofibromatosis is caused by mutations in the NF1 gene, which encodes neurofibromin, a large protein that modulates the activity of Ras. Here, we describe the identification and characterization of zebrafish nf1a and nf1b, orthologues of NF1, and show neural crest and cardiovascular defects resulting from morpholino knockdown, including vascular and cardiac valvular abnormalities. Development of a zebrafish model of von Recklinghausen neurofibromatosis will allow for structure-function analysis and genetic screens in this tractable vertebrate system.
We investigated changes in UV attenuation and macrozooplankton community structure in a set of lakes along a deglaciation chronosequence in Glacier Bay Alaska. Terrestrial succession in the ...watersheds of these lakes results in increasing dissolved organic carbon (DOC) content over time. Due to the primary role of DOC in controlling UV attenuation in lakes, one would suspect a gradient in UV attenuation and potentially zooplankton community structure in lakes of different ages. Field measurements of UV in seven lakes of different ages revealed that UV attenuation depths (1% of surface irradiance at 320 nm) ranged from 0.6 m in the oldest lake in the set (90 yr old), to more than 14 m in the youngest lake (10 yr old). Zooplankton community structure also changed across lakes of different ages. Patterns of distribution and abundance of the zooplankton both among and within lakes were consistent with the hypothesis that UV influences zooplankton community structure. The major differences in species composition among lakes were the absence of two primarily epilimnetic species (Asplanchna priodonta and Ceriodaphnia quadrangula) in all but the oldest lake, and the absence of Bosmina longirostris in the four youngest lakes. Transplant experiments in which UV radiation was manipulated in situ revealed that all three of these "delayed colonizer" species perish within only a few days when exposed to UV levels found in the surface waters (0.5 m depth) of the youngest lake. The strong dependence of UV radiation transparency on terrestrially derived DOC suggests a linkage between development of terrestrial plant communities within the watershed, changes in lake hydrology, and the early succession of zooplankton communities following deglaciation.
New technologies and analysis methods are enabling genomic structural variants (SVs) to be detected with ever-increasing accuracy, resolution and comprehensiveness. To help translate these methods to ...routine research and clinical practice, we developed a sequence-resolved benchmark set for identification of both false-negative and false-positive germline large insertions and deletions. To create this benchmark for a broadly consented son in a Personal Genome Project trio with broadly available cells and DNA, the Genome in a Bottle Consortium integrated 19 sequence-resolved variant calling methods from diverse technologies. The final benchmark set contains 12,745 isolated, sequence-resolved insertion (7,281) and deletion (5,464) calls ≥50 base pairs (bp). The Tier 1 benchmark regions, for which any extra calls are putative false positives, cover 2.51 Gbp and 5,262 insertions and 4,095 deletions supported by ≥1 diploid assembly. We demonstrate that the benchmark set reliably identifies false negatives and false positives in high-quality SV callsets from short-, linked- and long-read sequencing and optical mapping.
ABSTRACT
Background and objective: In patients with IPF, we sought to validate that abnormal heart rate recovery at 1 min (HRR1) after six‐minute walk test (6MWT) predicts mortality and to explore ...the relationship between abnormal HRR1 and pulmonary hypertension (PH).
Methods: We identified IPF patients who performed a 6MWT as part of their clinical evaluation between 2006 and 2009 and were followed to lung transplantation or death. Right heart catheterization (RHC) data were collated and analysed for the subgroup who had this procedure.
Results: There were 160 subjects who qualified for the survival analysis, and those with an abnormal HRR1 had worse survival than subjects with normal HRR1 (log‐rank P = 0.01). Eighty‐two subjects had a right heart catheter (RHC); among them, abnormal HRR1 was associated with RHC‐confirmed PH (χ2 = 4.83, P = 0.03) and had a sensitivity, specificity, positive predictive value and negative predictive value of 52%, 74%, 41% and 82%, respectively, for PH. In bivariate and multivariable analyses, abnormal HRR1 appeared to be the strongest predictor of RHC‐confirmed PH (odds ratio (OR) = 4.0, 95% CI: 1.17–13.69, P = 0.02 in the multivariable analysis).
Conclusions: This study adds to data that support the validity of abnormal HRR1 as a predictor of mortality and of RHC‐confirmed PH in IPF. Research is needed to further investigate the link between abnormal HRR1 and PH and to elucidate heart–lung interactions at work during exercise and recovery in patients with IPF.
For patients with IPF, a failure of heart rate to reduce by at least 14 beats/min after the first minute of recovery following completion of a six‐minute walk test is an independent predictor of mortality and of pulmonary hypertension.
•Sequencing results were in agreement for biologically conserved positions.•For biologically variable positions, sequencing depth impacted precision.•Results were biased by the algorithm used to ...align reads to the reference.
This study presents the results from an interlaboratory sequencing study for which we developed a novel high-resolution method for comparing data from different sequencing platforms for a multi-copy, paralogous gene. The combination of PCR amplification and 16S ribosomal RNA gene (16S rRNA) sequencing has revolutionized bacteriology by enabling rapid identification, frequently without the need for culture. To assess variability between laboratories in sequencing 16S rRNA, six laboratories sequenced the gene encoding the 16S rRNA from Escherichia coli O157:H7 strain EDL933 and Listeria monocytogenes serovar 4b strain NCTC11994. Participants performed sequencing methods and protocols available in their laboratories: Sanger sequencing, Roche 454 pyrosequencing®, or Ion Torrent PGM®. The sequencing data were evaluated on three levels: (1) identity of biologically conserved position, (2) ratio of 16S rRNA gene copies featuring identified variants, and (3) the collection of variant combinations in a set of 16S rRNA gene copies. The same set of biologically conserved positions was identified for each sequencing method. Analytical methods using Bayesian and maximum likelihood statistics were developed to estimate variant copy ratios, which describe the ratio of nucleotides at each identified biologically variable position, as well as the likely set of variant combinations present in 16S rRNA gene copies. Our results indicate that estimated variant copy ratios at biologically variable positions were only reproducible for high throughput sequencing methods. Furthermore, the likely variant combination set was only reproducible with increased sequencing depth and longer read lengths. We also demonstrate novel methods for evaluating variable positions when comparing multi-copy gene sequence data from multiple laboratories generated using multiple sequencing technologies.
Abstract Here, we detail in-progress genome-scale measurements from a variety of technologies of the first tumor normal benchmark from the Genome in a Bottle (GIAB) consortium. We created the first ...broadly-consented tumor cell line from a pancreatic ductal adenocarcinoma with matched normal pancreatic and duodenal tissue. Data is being collected from a large homogeneous batch of the tumor cell line and paired normal tissues. As we receive data we make it publicly available on the NCBI hosted GIAB FTP site, https://ftp.ncbi.nlm.nih.gov/ReferenceSamples/giab/data_somatic/. When complete, this dataset will include WGS measurements from Illumina, ONT, Hi-C, Bionano, single cell WGS, PacBio HiFi and Onso, and Element. Analysis and development of a variant calling benchmark using this data is ongoing in collaboration with an open working group of the GIAB consortium. Initial Hi-C and optical mapping data from the tumor cell line indicates substantial aneuploidy from translocations that cause large deletions. We found roughly 17 large inversions and translocations and 16 chromosomes with extensive loss of heterozygosity due to missing >30% of one copy, in addition to a few smaller duplications. Low coverage single cell sequencing that provides ploidy estimates across chromosomes showed that most of the large deletions appear in all or nearly all cells with some variation in a few cells. These observations are consistent with bulk WGS analyses from two batches of cells. Additionally, many of the observed large deletions correspond to deletions seen in the population of TCGA chromosomal Loss of Heterogeneity samples. Examining somatic SNVs in non-repetitive regions, we find that close to 60% occur in almost all cells in diploid regions, 30% occur in almost all cells in haploid regions, and 5% in only some cells in diploid and haploid regions, respectively. We take these results to indicate the cell line is relatively homogeneous and stable with most CNVs being deletions. As such, we plan to explore using long reads, ultralong reads, and Hi-C data to generate a near-complete genome assembly of the dominant tumor clone as well as a complete diploid assembly of the normal. With this personalized genome assembly, we will explore aligning tumor and normal reads to each haplotype of the normal to characterize somatic variants, including variants in minor clones. Building on the methods GIAB and T2T have developed to polish diploid assemblies of GIAB’s normal genomes and mosaic variant characterization, we will develop benchmarks for somatic variants against the normal assembly as well as standard references. Citation Format: Justin Wagner, Jennifer McDaniel, Gail L. Rosen, Nathan D. Olson, Vaidehi Patel, Chunlin Xiao, Andrew Liss, Justin Zook. Continued analysis of extensive data towards Genome in a Bottle benchmarks for a new tumor normal pair abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3551.
The precisionFDA Truth Challenge V2 aimed to assess the state of the art of variant calling in challenging genomic regions. Starting with FASTQs, 20 challenge participants applied their ...variant-calling pipelines and submitted 64 variant call sets for one or more sequencing technologies (Illumina, PacBio HiFi, and Oxford Nanopore Technologies). Submissions were evaluated following best practices for benchmarking small variants with updated Genome in a Bottle benchmark sets and genome stratifications. Challenge submissions included numerous innovative methods, with graph-based and machine learning methods scoring best for short-read and long-read datasets, respectively. With machine learning approaches, combining multiple sequencing technologies performed particularly well. Recent developments in sequencing and variant calling have enabled benchmarking variants in challenging genomic regions, paving the way for the identification of previously unknown clinically relevant variants.
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•Sixty-four submissions employing innovative variant-calling methods for three technologies•Submissions evaluated with new GIAB benchmark sets and new genome stratifications•Submissions differ in performance overall and in challenging genomic regions•Challenge data are available at https://doi.org/10.18434/mds2-2336
Olson et al. report on the results of precisionFDA Truth Challenge V2 for variant-calling pipelines. The challenge focused on small-variant accuracy of innovative deep learning and graph-based methods, utilizing a new benchmark and with new stratifications to demonstrate strengths and weaknesses of different methods.
Post-transplant lymphoproliferative disorder (PTLD) is a frequent and often fatal complication of organ transplantation. It most often results from an Epstein-Barr virus (EBV)-transformed B-cell ...clone, which expresses B-cell surface markers such as CD20. We describe a case of a heart transplant recipient who EBV seroconverted post-transplant and subsequently developed subcutaneous and lymphatic B-cell lymphoma, successfully treated with CD20 antibody (rituximab). The patient has been in remission during 10 months of clinical follow-up.
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