ABSTRACT
The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in SARS-CoV-2 genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length, and are thus infeasible for coronaviruses, which possess the longest genomes ([~]30,000 nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scales linearly with sequence length, enabling unprecedented global structural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurbo-Folds purely in silico prediction not only is close to experimentally-guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5 and 3 UTRs ([~]29,800 nt apart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies novel conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, siRNAs, CRISPR-Cas13 guide RNAs and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies, and will be a useful tool in fighting the current and future pandemics. Significance StatementConserved RNA structures are critical for designing diagnostic and therapeutic tools for many diseases including COVID-19. However, existing algorithms are much too slow to model the global structures of full-length RNA viral genomes. We present LinearTurboFold, a linear-time algorithm that is orders of magnitude faster, making it the first method to simultaneously fold and align whole genomes of SARS-CoV-2 variants, the longest known RNA virus ([~]30 kilobases). Our work enables unprecedented global structural analysis and captures long-range interactions that are out of reach for existing algorithms but crucial for RNA functions. LinearTurboFold is a general technique for full-length genome studies and can help fight the current and future pandemics.
ABSTRACT
SummaryCOVID-19 has become a global pandemic not long after its inception in late 2019. SARS-CoV-2 genomes are being sequenced and shared on public repositories at a fast pace. To keep up with these updates, scientists need to frequently refresh and reclean datasets, which is ad hoc and labor-intensive. Further, scientists with limited bioinformatics or programming knowledge may find it difficult to analyze SARS-CoV-2 genomes. In order to address these challenges, we developed CoV-Seq, a webserver to enable simple and rapid analysis of SARS-CoV-2 genomes. Given a new sequence, CoV-Seq automatically predicts gene boundaries and identifies genetic variants, which are presented in an interactive genome visualizer and are downloadable for further analysis. A command-line interface is also available for high-throughput processing. Availability and ImplementationCoV-Seq is implemented in Python and Javascript. The webserver is available at http://covseq.baidu.com/ and the source code is available from https://github.com/boxiangliu/covseq. Contactjollier.liu@gmail.com Supplementary informationSupplementary information are available at bioRxiv online.
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To analyze the efficiency of prenatal ultrasound screening service in Beijing and thus optimize the secondary prevention system for birth defects in Beijing. Data were collected from the prenatal screening work reports of Beijing from 2010-2016.Key variables were extracted after data quality control.Data envelopment analysis was performed to analyze the efficiency and changing trend of ultrasound-based screening service and to compare the service efficiency between urban and suburban areas in Beijing. From 2010 to 2016,the technical efficiency of ultrasound screening services showed an increasing trend,and the geometric mean of technical efficiency in suburban areas was higher than that in urban areas.From 2010 to 2016,the total factor productivity of ultrasound screening service increased by 12.3% annually,in which the technical change increased by 12.0% annually;the technical efficiency increased by 0.3%,the pure technical efficiency increased by 13.9% annually,and the scale efficiency decreased by 0.4%. The technical efficiency of ultrasound screening service in Beijing increased from 2010 to 2016,and the total factor productivity improved.Technical change and pure technical efficiency change were the main reasons for the improvement.The resource allocation should be further optimized to improve the scale efficiency and enhance the training of prenatal ultrasound screening technicians.
Subject(s)
Female , Humans , Pregnancy , Beijing , Mass Screening , Prenatal Diagnosis , Ultrasonography, PrenatalABSTRACT
Objective@#To investigate the influence of maternal age on the health status of pregnant women and the pregnant outcomes.@*Methods@#Data obtained from "Beijing perinatal health management registration system" was analyzed, 263 157 pregnant women with age information were included from October 1st, 2015 to September 30th, 2016, in which 43 594 women delivered at the age of 35 or above (advanced age) . According to the age of maternal age, there were 5 groups. (1) Proper age: 219 563 (83.43%, 219 563/263 157) cases of the age of 18-34 years, including 122 735 cases (46.64%, 122 735/263 157) in the ≤29 years old group and 96 828 cases (36.79%, 96 828/263 157) in 30-34 years old group. (2) Advanced age: there were 43 594 cases (16.57%, 43 594/263 157) ≥35 years old, including 37 395 cases (14.21%, 37 395/263 157) in the 35-39 years old group, 5 790 cases (2.20%, 5 790/263 157) in the 40-44 years old group and 409 cases (0.16%, 409/263 157) in the ≥45 years old group. The trend-based chi-square test and logistic regression were used to analyze the effects of different age groups on maternal complications and pregnant outcomes.@*Results@#(1) The total incidence of high risk pregnancy (HRP) : in advanced age women, the incidence of HRP was 67.83% (29 571/43 594) which was 56.73% (124 550/219 563) in proper age women, the difference was statistically significant (χ2=1 848.91, P<0.000) . In advanced age women, the incidence of severe HRP was 7.64% (3 329/43 594) which was 6.18% (13 571/219 563) in proper age women, the difference was statistically significant (χ2=128.211, P<0.000) . In advanced age women, the incidence of very severe HRP was 1.76% (769/43 594) which was 0.84% (1 838/219 563) in proper age women, the difference was statistically significant (χ2=318.58, P<0.000) . (2) Comparison of the incidence of HRP in 5 groups:the total incidence of HRP increased through the following age group ≤29 years, 30-34 years, 35-39 years, 40-44 years, ≥45 years (53.28%, 61.09%, 67.41%、70.09%, 74.57% respectively) , the difference was statistically significant (linear by linear χ2=3 165.72, P<0.000) . The incidence of very severe HPR increased (0.66%, 1.06%, 1.66%, 2.35%, 2.93% respectively) , the difference was statistically significant (linear by linear χ2=218.31, P<0.000) . The incidence of severe HPR increased (5.77%, 6.70%, 7.48%, 8.34%, 11.49% respectively) , the difference was statistically significant (linear by linear χ2=422.20, P<0.000) . The incidence of general HPR increased (46.84%, 53.34%, 58.26%, 59.40%, 60.15% respectively) , the difference was statistically significant (linear by linear χ2=1 947.51, P<0.000) . (3) As the maternal age group increased, the incidence of adverse pregnancy outcomes increased (5.54%, 6.85%, 8.77%, 9.90%, 18.09%, linear by linear χ2=674.57, P<0.000) . The incidence of perinatal death, premature birth and low birth weight also presented the above trends (perinatal death: linear by linear χ2=34.79, P<0.000; premature birth: linear by linear χ2=692.87, P<0.000; low birth weight: linear by linear χ2=379.20, P<0.000) . (4) Logistic regression analysis with the assisted reproductive technology and multiple pregnancy considered showed the same trend (P<0.000) .@*Conclusion@#The maternal age has an impact on the maternal health status and pregnancy outcomes, and the risk of various types of pregnancy complications and adverse pregnancy outcomes increase with the maternal age group, antenatal care and management should be emphasized in women with advanced maternal age, especially for women ≥40 years old.
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Objective To investigate the status of second trimester maternal serum screening for Down's syndrome from 2006 to 2009 to evaluate the screening quality in Beijing.Methods Birth defect data (birth defect register) from 2006 to 2009 and screening data reported by certificated screening hospitals from 2008 to 2009 in Beijing were retrospectively analyzed by descriptive statistic method.Results Three hundred and thirty Down' syndrome babies were delivered from 2006 to 2009 in Beijing,among which 166 mothers accepted Down' syndrome serum screening and 85(51.2％) were diagnosed finally according to the screening results;among the 85 mothers,35 were≥35 years old with the detection rate of 62.5％ (35/56),and 50 cases were ＜35 with the detection rate of 45.5％ (50/110).The prenatal diagnostic rate of Down's syndrome babies increased from 26.8％(11/41) in 2006 to 47.4％(46/97) in 2009.The detection rate of Down's syndrome with serum screening increased from 23.1％(3/13) in 2006 to 62.9％(22/35) in 2009.One hundred and fifty-eight 21-trisomy cases accepted mid-term ultrasound screening,among which 62 cases (39.2％) were found abnormal.Conclusions Quality control for second trimester maternal serum screening for Down's syndrome should be improved in Beijing.Second trimester maternal serum screening for Down's syndrome in elderly primipara is not suggested.More attention should be paid on prenatal ultrasound screening.
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Objective To evaluate the effect of standardized training and management of prenatal ultrasound screening on birth defects. Methods According to the degree of standardized training and management of prenatal ultrasound screening, the period from March 2004 to December 2009 were divided into three different management stages. Detection rate was applied to describe the prenatal ultrasound screening of 5199 birth defects cases delivered during the three different management stages. Accuracy rate was used to describe the ultrasonographic diagnosis made by staffs in 2009. SPSS 11.5 software was used to analyze the information of 707 staffs participated in the training and assessment activities from October 2007 to September 2009. Related factors of prenatal ultrasound operating skills of staffs were analyzed by comparing the distributing discrepancy of the different variables between qualified and unqualified group with Chi-square test. Results The detection rate of prenatal ultrasonographic screening on birth defects increased with the improvement of training and assessment methods, which was 32. 43% from March 2004 to September 2005,44.81% from October 2005 to September 2007 and 60. 71% from October 2007 to December 2009respectively. In 2009, 187 doctors were tested on abnormal ultrasound photographs identification. The accurate rates were 80. 0% for gastroschisis, 78. 8% for cleft clip, 75.8% for omphalocele, 71.8%for neural tube defects, 50. 0% for severe congenital heart diseases, 31.0% for acromicria, which were in similar sequence as the diagnostic rate identified by prenatal ultrasound in 2009. Among the staffs attending the prenatal ultrasound screening assessment, more had education background at least university level (52.8% vs 47.2%), more performed ≥50 ultrasound screenings per month (50. 5%vs 49.5 % ), more had been working on obstetric ultrasound over 3 yrs (52.5 % vs 47.5 %) and more had been trained in higher level of hospitals focused on prenatal diagnosis (64.7% vs 35.3%) in the qualified group than in the unqualified group. Conclusions Standardized training and management of prenatal ultrasonographic screening could effectively improve the diagnosis rate of birth defects.The quality of prenatal ultrasound screening is related to the staff's education background and whether they are engaged in the position.
