Similarities and Differences Between Variants Called With Human Reference Genome HG19 or HG38

Background: Reference genome selection is a prerequisite for successful analysis of next generation sequencing (NGS) data. Current practice employs one of the two most recent human reference genome versions: HG19 or HG38. To date, the impact of genome version on SNV identification has not been rigorously assessed. Results: We conducted analysis comparing the SNVs identified based on HG19 vs HG38, leveraging whole genome sequencing (WGS) data from the genome-in-a-bottle (GIAB) project. First, SNVs were called using 26 different bioinformatics pipelines with either HG19 or HG38. Next, two tools were used to convert the called SNVs between HG19 and HG38. Lastly we calculated conversion rates, analyzed discordant rates between SNVs called with HG19 or HG38, and characterized the discordant SNVs. Conclusions: The conversion rates from HG38 to HG19 (average 95%) were lower than the conversion rates from HG19 to HG38 (average 99%). The conversion rates varied slightly among the various calling pipelines. Around 1.5% SNVs were discordantly converted between HG19 or HG38. The conversions from HG38 to HG19 had more SNVs which failed conversion and more discordant SNVs than the opposite conversion (HG19 to HG38). Most of the discordant SNVs had low read depth, were low confidence SNVs as defined by GIAB, and/or were predominated by G/C alleles (52% observed versus 42% expected)

Leaf Extract of Eupatorium adenophorum negatively Regulates Growth of Alternanthera philoxeroides

Allelopathy is an important biological phenomenon in exotic plant invasions. Studies about this phenomenon can help us to understand how plant interactions influence plant colony and ecosystem functioning. Both alligator weed (Alternanthera philoxeroides, Ap) and crofton weed (Eupatorium adenophorum, Ea) are important destructive exotic species in China. Their allelopathic effects on native plant species are well documented. However, whether alligator weed and crofton weed antagonize each other regarding plant growth? There is largely unknown currently. Here we report that the leaf extract from crofton weed possesses the negative effect on the growth of alligator weed. The results showed that root growth of alligator weed could be seriously inhibited by aqueous extract from crofton weed, exhibited as no root or a few roots if only. Consistent with the inhibition of root growth, we observed changes of physiological and biochemical parameters in treated alligator weed. The chlorophyll content, the root activity and the acetolactate synthase (ALS) activity were significantly decreased; while the rate of superoxide anion (O2-), the malondialdehyde (MDA) content, the peroxidase (POD) activity, and the shikimic acid content were remarkably increased in the treated alligator weed plants. These physiological analyzes suggested that the main allelopathic effects of crofton weed were mainly through affecting the integrity of cell membrane and the activity of the key enzymes. Further, these data also imply that one exotic species has the potential value to be used in bio-control of the other exotic species

Efficacy of Chuanxiong Ding Tong Herbal Formula Granule in the Treatment and Prophylactic of Migraine Patients: A Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial

Objective. To evaluate the efficacy of traditional Chinese herbal ChuanXiong Ding Tong herbal formula granule (CXDT-HFG) for migraine patients with “the Syndrome of Liver Wind and Blood Stasis.” Methods. 150 migraine patients were recruited and assigned randomly in a double-blind, placebo-controlled study to receive CXDT-HFG (n=99) plus necessary analgesics, or placebo (n=51) plus necessary analgesics for 16 weeks (12 weeks’ intervention and 4 weeks’ follow up). Outcome measures included migraine days, frequency of migraine attacks, analgesics consumption for acute treatment, and the proportion of responders as well as the visual analogue scale (VAS) scores and intensity for pain. Results. Compared with the placebo group, the CXDT-HFG group showed significant reduction in migraine days and attacks frequency at week 12 and follow-up period (P0.05). Conclusion. CXDT-HFG was more effective than placebo in decreasing days of migraine attacks, frequency, VAS scores, and relieving pain intensity for migraine patients

Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma delta-T or NK cells

Peer reviewe

Assessing Reproducibility of Inherited Variants Detected With Short-Read Whole Genome Sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when \u3e 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30×. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS

Assessing reproducibility of inherited variants detected with short-read whole genome sequencing

Background: Reproducible detection of inherited variants with whole genome sequencing (WGS) is vital for the implementation of precision medicine and is a complicated process in which each step affects variant call quality. Systematically assessing reproducibility of inherited variants with WGS and impact of each step in the process is needed for understanding and improving quality of inherited variants from WGS. Results: To dissect the impact of factors involved in detection of inherited variants with WGS, we sequence triplicates of eight DNA samples representing two populations on three short-read sequencing platforms using three library kits in six labs and call variants with 56 combinations of aligners and callers. We find that bioinformatics pipelines (callers and aligners) have a larger impact on variant reproducibility than WGS platform or library preparation. Single-nucleotide variants (SNVs), particularly outside difficult-to-map regions, are more reproducible than small insertions and deletions (indels), which are least reproducible when > 5 bp. Increasing sequencing coverage improves indel reproducibility but has limited impact on SNVs above 30x. Conclusions: Our findings highlight sources of variability in variant detection and the need for improvement of bioinformatics pipelines in the era of precision medicine with WGS.Peer reviewe

Actively implementing an evidence-based feeding guideline for critically ill patients (NEED): a multicenter, cluster-randomized, controlled trial

Background: Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods: We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results: Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions: In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792. Registered November 20th, 2017