A cancer cell-line titration series for evaluating somatic classification.

BackgroundAccurate detection of somatic single nucleotide variants and small insertions and deletions from DNA sequencing experiments of tumour-normal pairs is a challenging task. Tumour samples are often contaminated with normal cells confounding the available evidence for the somatic variants. Furthermore, tumours are heterogeneous so sub-clonal variants are observed at reduced allele frequencies. We present here a cell-line titration series dataset that can be used to evaluate somatic variant calling pipelines with the goal of reliably calling true somatic mutations at low allele frequencies.ResultsCell-line DNA was mixed with matched normal DNA at 8 different ratios to generate samples with known tumour cellularities, and exome sequenced on Illumina HiSeq to depths of >300×. The data was processed with several different variant calling pipelines and verification experiments were performed to assay >1500 somatic variant candidates using Ion Torrent PGM as an orthogonal technology. By examining the variants called at varying cellularities and depths of coverage, we show that the best performing pipelines are able to maintain a high level of precision at any cellularity. In addition, we estimate the number of true somatic variants undetected as cellularity and coverage decrease.ConclusionsOur cell-line titration series dataset, along with the associated verification results, was effective for this evaluation and will serve as a valuable dataset for future somatic calling algorithm development. The data is available for further analysis at the European Genome-phenome Archive under accession number EGAS00001001016. Data access requires registration through the International Cancer Genome Consortium's Data Access Compliance Office (ICGC DACO)

Development of a Next-Generation NIL Library in Arabidopsis Thaliana for Dissecting Complex Traits

The identification of the loci and specific alleles underlying variation in quantitative traits is an important goal for evolutionary biologists and breeders. Despite major advancements in genomics technology, moving from QTL to causal alleles remains a major challenge in genetics research. Near-isogenic lines are the ideal raw material for QTL validation, refinement of QTL location and, ultimately, gene discovery. Results: In this study, a population of 75 Arabidopsis thaliana near-isogenic lines was developed from an existing recombinant inbred line (RIL) population derived from a cross between physiologically divergent accessions Kas-1 and Tsu-1. First, a novel algorithm was developed to utilize genome-wide marker data in selecting RILs fully isogenic to Kas-1 for a single chromosome. Seven such RILs were used in 2 generations of crossing to Tsu-1 to create BC1 seed. BC1 plants were genotyped with SSR markers so that lines could be selected that carried Kas-1 introgressions, resulting in a population carrying chromosomal introgressions spanning the genome. BC1 lines were genotyped with 48 genome-wide SSRs to identify lines with a targeted Kas-1 introgression and the fewest genomic introgressions elsewhere. 75 such lines were selected and genotyped at an additional 41 SNP loci and another 930 tags using 2b-RAD genotyping by sequencing. The final population carried an average of 1.35 homozygous and 2.49 heterozygous introgressions per line with average introgression sizes of 5.32 and 5.16 Mb, respectively. In a simple case study, we demonstrate the advantage of maintaining heterozygotes in our library whereby fine-mapping efforts are conducted simply by self-pollination. Crossovers in the heterozygous interval during this single selfing generation break the introgression into smaller, homozygous fragments (sub-NILs). Additionally, we utilize a homozygous NIL for validation of a QTL underlying stomatal conductance, a low heritability trait. Conclusions: The present results introduce a new and valuable resource to the Brassicaceae research community that enables rapid fine-mapping of candidate loci in parallel with QTL validation. These attributes along with dense marker coverage and genome-wide chromosomal introgressions make this population an ideal starting point for discovery of genes underlying important complex traits of agricultural and ecological significance.NSF DEB-1022196, DEB-0618302, DEB-0618347, IOS-09221457Integrative Biolog

Quantitative trait loci controlling agronomic and biochemical traits in \u3ci\u3eCannabis sativa\u3c/i\u3e

Understanding the genetic basis of complex traits is a fundamental goal of evolutionary genetics. Yet, the genetics controlling complex traits in many important species such as hemp (Cannabis sativa) remain poorly investigated. Because hemp’s change in legal status with the 2014 and 2018 U.S. Federal Farm Bills, interest in the genetics controlling its numerous agriculturally important traits has steadily increased. To better understand the genetics of agriculturally important traits in hemp, we developed an F2 population by crossing two phenotypically distinct hemp cultivars (Carmagnola and USO31). Using whole-genome sequencing, we mapped quantitative trait loci (QTL) associated with variation in numerous agronomic and biochemical traits. A total of 69 loci associated with agronomic (34) and biochemical (35) trait variation were identified. We found that most QTL co-localized, suggesting that the phenotypic distinctions between Carmagnola and USO31 are largely controlled by a small number of loci. We identified TINY and olivetol synthase as candidate genes underlying colocalized QTL clusters for agronomic and biochemical traits, respectively. We functionally validated the olivetol synthase candidate by expressing the alleles in yeast. Gas chromatography-mass spectrometry assays of extracts from these yeast colonies suggest that the USO31 olivetol synthase is functionally less active and potentially explains why USO31 produces lower cannabinoids compared to Carmagnola. Overall, our results help modernize the genomic understanding of complex traits in hemp

Comparing Sex-Specific Outcomes After Rotator Cuff Repair: A Meta-analysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Rotator cuff repair (RCR) is a well-studied procedure. However, the impact of patient sex on outcomes after RCR has not been well studied. Purpose: To conduct a systematic review and meta-analysis of sex-based differences in outcomes after RCR and to record what proportion of studies examined this as a primary or secondary purpose. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using multiple databases according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies were included if they were written in English, performed on humans, consisted of patients who underwent RCR, evaluated at least 1 of the selected outcomes based on patient sex, and had statistical analysis available for their sex-based claim. Excluded were case reports, review studies, systematic reviews, cadaveric studies, and studies that did not report at least 1 sex-specific outcome or included certain other injuries associated with a rotator cuff injury. Results: Of 9998 studies screened and 1283 full-text studies reviewed, 11 (0.11%) studies with 2860 patients (1549 male and 1329 female) were included for quantitative analysis. None of these 11 studies examined the impact of patient sex on outcomes after RCR as a primary outcome. Postoperative Constant-Murley scores were analyzed for 7 studies. Male patients had a postoperative Constant-Murley score of 76.77 ± 15.94, while female patients had a postoperative Constant-Murley score of 69.88 ± 17.02. The random-effects model showed that male patients had significantly higher scores than female patients, with a mean difference of 7.33 (95% CI, 5.21-9.46; P < .0001). Analysis of retear rates in 5 studies indicated that there was no difference in the retear rate between sexes (odds ratio, 0.91 [95% CI, 0.49-1.67]). Conclusion: Female patients had lower postoperative Constant-Murley scores compared with male patients, but there was no difference in the retear rate. However, these results were based on an analysis of only 11 studies. The paucity of studies examining the impact of sex suggests that more research is needed on the impact of patient sex on outcomes after RCR

Return to Sport After Turf Toe Injuries: A Systematic Review and Meta-analysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: The prevalence of turf toe injuries has increased in recent years. However, uncertainty remains as to how to optimally treat turf toe injuries and the implications that the severity of the injury has on outcomes, specifically return to sport (RTS). Purpose: To determine RTS based on treatment modality and to provide clinicians with additional information when comparing operative versus nonoperative treatment of turf toe injuries in athletes. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review and meta-analysis was performed using the PubMed/Ovid MEDLINE/PubMed Central databases (May 1964 to August 2018) per PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data) guidelines. RTS, treatment, severity of injury, athletic position, and sport were recorded and analyzed. Results: Of 858 identified studies, 12 met the criteria for the final meta-analysis. The studies included 112 athletes sustaining a total of 121 turf toe injuries; 63 (52.1%) of these injuries were treated surgically, while 58 (47.9%) were treated nonoperatively, and 53.7% were classified by the grade of injury (grade I, n = 1; grade II, n = 9; grade III, n = 55). Overall, 56 (46.3%) injuries could not be classified based on the data provided and were excluded from the final analysis. The median time to RTS for patients treated nonoperatively was 5.85 weeks (range, 3.00-8.70 weeks) compared with 14.70 weeks (range, 6.00-156.43 weeks) for patients treated surgically (P < .001); however, there was variability in the grade of injury between the 2 groups. Similarly, patients who sustained grade II injuries returned to sport more quickly (8.70 weeks) than patients who had a grade I (13.04 weeks) or grade III injury (16.50 weeks) (P = .016). The amount of time required to RTS was significantly influenced by the athlete’s level of play (16.50 weeks for both high school and college levels; 14.70 weeks for professional level) (P = .018). Conclusion: The time to RTS for an athlete who suffers from a turf toe injury is significantly influenced by the severity of injury and the athlete’s level of competition. Professional athletes who suffer from turf toe injuries RTS sooner than both high school and college athletes. However, there are a limited number of high-level studies evaluating turf toe injuries in the athletic population. Further research is necessary to clearly define the appropriate treatment and RTS protocols based on sport, position, and level of play

Sex-Specific Outcomes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Despite the significant difference between men and women in incidence of anterior cruciate ligament (ACL) injuries, there is a paucity of consistent information on the influence of patient sex on outcomes after ACL reconstruction. A previous meta-analysis has demonstrated that female patients have worse outcomes with regard to laxity, revision rate, Lysholm score, and Tegner activity score and are less likely to return to sports (RTS). Purpose: To conduct a systematic review and meta-analysis to evaluate and compare sex-specific outcomes after ACL reconstruction. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed using PubMed, PubMed Central, Embase, OVID, and Cochrane databases per PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The following search terms were used: “anterior cruciate ligament reconstruction” OR “ACL reconstruction” OR “anterior cruciate ligament” OR “ACL” AND “gender” OR “sex” OR “male” OR “female” AND “outcome” AND “2015-Present” to gather all relevant articles between 2015 and 2020. A risk-of-bias assessment and quality assessment was conducted on included studies. Results: Of 9594 studies initially identified, 20 studies with 35,935 male and 21,455 female patients were included for analysis. The 7 studies reporting International Knee Documentation Committee (IKDC) scores showed that male patients had statistically significantly higher postoperative scores (mean difference, 3.02 [95% CI, 1.19-4.84]; P< .01; I 2 = 66%), and 7 studies that reported the rate of ACL revision showed there was no significant difference between male and female patients (odds ratio, 0.85 [95% CI, 0.45-1.60]; P = .61; I 2 = 94%). The 7 studies that reported rates of rerupture showed that males were significantly more likely than females to have a graft rerupture (odds ratio, 1.35 [95% CI, 1.22-1.50]; P < .01; I 2 = 0%). Male patients reported a higher RTS rate than did their female counterparts (59.82% compared with 42.89%); however, no formal statistical analysis could be done because of the variability in reporting techniques. Conclusion: Male and female patients with ACL injuries demonstrated similar outcomes regarding their rates of revision; however, male patients were found to have statistically significantly higher postoperative IKDC scores but at the same time higher rerupture rates. Our findings suggest that sex-based differences in outcomes after ACL reconstruction vary based on which metric is used. These results must be considered when counseling patients with ACL injuries

Sex-Based Differences in Outcomes After Hip Arthroscopic Surgery for Femoroacetabular Impingement: A Systematic Review

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: While sex-based differences in outcomes after hip arthroscopic surgery for femoroacetabular impingement syndrome (FAIS) are often recorded, no studies have been dedicated to analyzing the literature as a whole. Purpose: To investigate whether sex is a predictor of outcomes in studies evaluating hip arthroscopic surgery for FAIS. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched the PubMed, Embase, Cochrane, Ovid, and PubMed Central databases for English-language studies that evaluated sex-specific outcomes in human populations. The search terms used were as follows: (“Hip Arthroscopy”) AND (“Femoroacetabular Impingement” OR “FAI”) AND (“Sex” OR “Gender” OR “Male” OR “Female”). Studies with evidence levels 2 through 4 were included. The studies were then screened, followed by data extraction. Modified Harris Hip Score (mHHS) outcomes and return-to-sport (RTS) rates were recorded. These were analyzed using random-effects meta-analysis. Heterogeneity was calculated using the I2 statistic. Results: Of 256 full-text articles screened, 48 articles were included in this analysis; of these, 14 studies (29%) concluded that female sex was a negative predictor of postoperative outcomes, while 6 studies (13%) found female sex to be positive predictor. The remaining 28 studies (58%) found no sex-based differences in postoperative outcomes. Of 7 studies (416 male and 519 female) included in the mHHS analysis, 2 studies concluded that male patients had significantly higher postoperative mHHS scores. Of 6 studies (502 male and 396 female) included in the RTS analysis, 1 study concluded that male patients had a significantly higher RTS rate. Conclusion: Almost one-third of the included studies determined that female sex was a negative predictor of postoperative outcomes, 13% found female sex to be a positive predictor, and 58% found no sex-based differences. Our study illustrates an insufficiency of high-level evidence supporting sex-specific differences in outcomes after hip arthroscopic surgery, but findings indicated that the postoperative mHHS score and RTS rate may be influenced by sex

Zero Frequency Current Noise for the Double Tunnel Junction Coulomb Blockade

We compute the zero frequency current noise numerically and in several limits analytically for the coulomb blockade problem consisting of two tunnel junctions connected in series. At low temperatures over a wide range of voltages, capacitances, and resistances it is shown that the noise measures the variance in the number of electrons in the region between the two tunnel junctions. The average current, on the other hand, only measures the mean number of electrons. Thus, the noise provides additional information about transport in these devices which is not available from measuring the current alone.Comment: 33 pages, 10 figure

Identification of a New Class of Lipid Droplet-Associated Proteins in Plants

Article on the identification of a new class of lipid droplet-associated proteins in plants

Pervasive brain monitoring and data sharing based on multi-tier distributed computing and linked data technology

EEG-based Brain-computer interfaces (BCI) are facing grant challenges in their real-world applications. The technical difficulties in developing truly wearable multi-modal BCI systems that are capable of making reliable real-time prediction of users’ cognitive states under dynamic real-life situations may appear at times almost insurmountable. Fortunately, recent advances in miniature sensors, wireless communication and distributed computing technologies offered promising ways to bridge these chasms. In this paper, we report our attempt to develop a pervasive on-line BCI system by employing state-of-art technologies such as multi-tier fog and cloud computing, semantic Linked Data search and adaptive prediction/classification models. To verify our approach, we implement a pilot system using wireless dry-electrode EEG headsets and MEMS motion sensors as the front-end devices, Android mobile phones as the personal user interfaces, compact personal computers as the near-end fog servers and the computer clusters hosted by the Taiwan National Center for High-performance Computing (NCHC) as the far-end cloud servers. We succeeded in conducting synchronous multi-modal global data streaming in March and then running a multi-player on-line BCI game in September, 2013. We are currently working with the ARL Translational Neuroscience Branch and the UCSD Movement Disorder Center to use our system in real-life personal stress and in-home Parkinson’s disease patient monitoring experiments. We shall proceed to develop a necessary BCI ontology and add automatic semantic annotation and progressive model refinement capability to our system