The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated networ...The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated network,including RNA-RNA relationships and RNA-RNA binding protein(RNA-RBP)relationships.We use the parameter framework technology proposed in this paper to screen differentially expressed circRNA,messenger RNA(mRNA),and microRNA(miRNA)from the expression profile of samples related to HCM.And 31 pairs of circRNA and mRNA relationship pairs were extracted,combined with the miRNA targeting database;145 miRNA-mRNA relationship pairs were extracted;268 circRNA-mRNA-miRNA triads were established through the common mRNA in the 2 types of relationship pairs.Thus,268 circRNA-miRNA regulatory relationships were deduced and 30 circRNARBP relationship pairs were analyzed at the protein level.On this basis,a circRNA-mediated regulatory network corresponding to the two levels of RNA-RNA and RNA-RBP was established.And then the roles of circRNA in HCM were analyzed through circRNA-mRNA,circRNA-miRNA,and circRNA-RBP,and the possible role in disease development mas inferred.展开更多
The studies on clutter modeling and suppression of airborne radar with a parabolic conformal array are uncommon due to the complexity of this type of antenna array configuration.The correct understanding of clutter ch...The studies on clutter modeling and suppression of airborne radar with a parabolic conformal array are uncommon due to the complexity of this type of antenna array configuration.The correct understanding of clutter characteristics for airborne radar with a parabolic conformal antenna array is the prerequisite and foundation of optimal suppression of this type of clutter.This paper establishes the model of clutter echo of airborne parabolic conformal phased array radar and analyzes the structure characteristics and the distribution features of this type of clutter.The simulation results show that this type of clutter has the following characteristics:1) The main lobe on the azimuth is seriously broadened,2) the power spectrum presents strong heterogeneity,and 3) the freedom degrees are high.Based on the existing related clutter suppression methods,we verified the correctness of the constructed clutter model.This work has an important guidance to further study on clutter suppression methods in airborne parabolic conformal array radar.展开更多
The biological features of the valvular heart disease with atrial fibrillation(AF-VHD)remain unknown when involving long non-coding RNAs(lncRNAs).This study performed system analysis on lncRNA and messenger RNA(mRNA)e...The biological features of the valvular heart disease with atrial fibrillation(AF-VHD)remain unknown when involving long non-coding RNAs(lncRNAs).This study performed system analysis on lncRNA and messenger RNA(mRNA)expression profiles constructed by using bioinformatics methods and tools for biological features of AF-VHD.Fold change and t-test were used to identify differentially expressed(DE)lncRNAs and mRNAs.The enrichment analysis of DE mRNAs was performed.The subgroups formed by lncRNAs and nearby mRNAs were screened,and a transcriptional regulation network among lncRNAs,mRNAs,and transcription factors(TFs)was constructed.The interactions between mRNAs related to lncRNAs and drugs were predicted.The 620 AF-VHDrelated DE lncRNAs and 452 DE mRNAs were identified.The 3 lncRNA subgroups were screened.The 665 regulations mediated by lncRNAs and TFs were identified.The 9 mRNAs related to lncRNAs had 1 or more potential drug interactions,totaling 37 drugs.Of these,9 drugs targeting 3 genes are already known to be able to control or trigger atrial fibrillation(AF)or other cardiac arrhythmias.The found biological features of AF-VHD provide foundations for further biological experiments to better understand the roles of lncRNAs in development from the valvular heart disease(VHD)to AF-VHD.展开更多
Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine,especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in c...Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine,especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in clinical trials is also very important. In many cases, the patient's immune level is relatively low, so we first studied the safety assessment of plasma treatment in an immunocompromised animal model. In this study, we examined the safety of immuno-deficient nude mice by oral lavage treatment of plasma-activated water, and studied the growth status, main organs and blood biochemical indexes. Acute toxicity test results showed that the maximum dose of plasma treatment for 15 min had no lethal effect and other acute toxicity. There were no significant changes in body weight and survival status of mice after 2 min and 4 min of plasma-activated water(PAW)treatment for 2 weeks. After treatment, the major organs, including heart, liver, spleen, lung and kidney, were not significantly changed in organ coefficient and tissue structure. Blood biochemical markers showed that blood neutrophils and mononuclear cells were slightly increased, and the others remained unchanged. Liver function, renal function, electrolytes, glucose metabolism and lipid metabolism were not affected by different doses of PAW treatment. The above results indicate that PAW treatment can be used to treat immuno-deficient nude mice without significant safety problems.展开更多
In this study,we investigated the effects of the quartz tube diameter,air flow rate,and applied voltage on the characteristics of an air plasma jet to obtain the optimized discharge characteristics.The physicochemical...In this study,we investigated the effects of the quartz tube diameter,air flow rate,and applied voltage on the characteristics of an air plasma jet to obtain the optimized discharge characteristics.The physicochemical properties and concentration of reactive oxygen and nitrogen species(RONS)in plasma-activated medium(PAM)were characterized to explore their chemical activity.Furthermore,we investigated the inactivation effect of air plasma jet on tumour cells and their corresponding inactivation mechanism.The results show that the tube diameter plays an important role in sustaining the voltage of the air plasma jet,and the gas flow rate affects the jet length and discharge intensity.Additionally,the air plasma jet discharge displays two modes,namely,ozone and nitrogen oxide modes at high and low gas flow rates,respectively.Increasing the voltage increases the concentration of reactive species and the length of discharge.By evaluating the viability of A549 cells under different parameters,the optimal treatment conditions were determined to be a quartz tube diameter of 4 mm,gas flow rate of 0.5 SLM,and voltage of 18 k V.Furthermore,an air plasma jet under the optimized conditions effectively enhanced the chemical activity in PAM and produced more aqueous RONS.The air plasma jet induced significant cytotoxicity in A549 cancer cells after plasma treatment.H_(2)O_(2) and NO_(2) are regarded as key factors in promoting cell inactivation.The present study demonstrates the potential use of tumour cell therapy by atmospheric air PAM,which aids a better understanding of plasma liquid chemistry.展开更多
Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are expose...Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.展开更多
Genomic islands(Gis)are one of the most important components for cyanobacterial genome.The Gis code has many functions,such as symbiosis,pathogenesis,and adaptation.In this article,we predict and analyze the Gis in Sy...Genomic islands(Gis)are one of the most important components for cyanobacterial genome.The Gis code has many functions,such as symbiosis,pathogenesis,and adaptation.In this article,we predict and analyze the Gis in Synechocystis sp.PCC 6803 by bioinfomatics,and the results show that ISL1,ISL8,and ISL16 are homologous with many other bacteria,and they involve in basic reactions and have a conservative evolution.On the contrary,ISL15 has a unique sequence and function only for Synechocystis sp.PCC6803.Most of Gis play a role in genome rearrangement because they have lots of transposase.Moreover,we find that recombination and horizontal transfer of Gis are important factors to affect the distribution of non-coding RNA.Our work contributes to a comprehensive understanding of genomic islands and their impact on genome of cyanobacteria.展开更多
Dear Editor,Traffic driving is a dynamic and complicated task in which drivers are required to pay close attention to the important targets or regions to maintain safe margins.Rainy weather conditions make it more cha...Dear Editor,Traffic driving is a dynamic and complicated task in which drivers are required to pay close attention to the important targets or regions to maintain safe margins.Rainy weather conditions make it more challenging with factors such as low visibility,raindrops,pedestrian with umbrellas,wipers,etc.Studies showed that rainy condition affects driving safety significantly[1],[2].It is reported that,in raining weather condition,the odds for a fatal accident are 3.340 times higher on highways than on streets[3].An investigation of the relationship between rainfall and fatal crashes in Texas from 1994 to 2018 on fatality analysis reporting system(FARS)database illustrated that rain-related fatal crashes represented about 6.8%of the total fatal crashes on average,moreover,the proportion showed high variability at the annual,monthly,and hourly time scales[4].Therefore,raining is a complex and critical factor for road safety planning and management.In fact,the traffic environment is a dynamic scene with multiple sources of information,including important targets that are highly relevant to the current driving task as well as irrelevant targets that may distract the driving task[5].展开更多
Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play...Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.展开更多
The world has entered an era featured with fast transportations,instant communications,and prompt technological revolutions,the further advancement of which all relies fundamentally,yet,on the development of cost-effe...The world has entered an era featured with fast transportations,instant communications,and prompt technological revolutions,the further advancement of which all relies fundamentally,yet,on the development of cost-effective energy resources allowing for durable and high-rate energy supply.Current battery and fuel cell systems are challenged by a few issues characterized either by insufficient energy capacity or by operation instability and,thus,are not ideal for such highly-demanded applications as electrical vehicles and portable electronic devices.In this mini-review,we present,from materials perspectives,a few selected important breakthroughs in energy resources employed in these applications.Prospectives are then given to look towards future research activities for seeking viable materials solutions for addressing the capacity,durability,and cost shortcomings associated with current battery/fuel cell devices.展开更多
Every human being looks different in one way or the other.That’s the work of genetic variations,the ultimate driving force for evolution as well as the cause for many human diseases.Mapping human genetic variants rev...Every human being looks different in one way or the other.That’s the work of genetic variations,the ultimate driving force for evolution as well as the cause for many human diseases.Mapping human genetic variants reveals global genetic diversity,and pinpoints causal variants behind genetic disorders.展开更多
Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.However,detecting the compounded mutational...Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.However,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery compared with simple structural variants.Here,we systematically analyzed the multi-breakpoint connection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.展开更多
基金the National Natural Science Foundation of China under Grant No.61872405the Key R&D program of Sichuan Province under Grant No.2020YFS0243the Key Project of Natural Science Foundation of Guangdong Province under Grant No.2016A030311040.
文摘The pathogenesis of hypertrophic cardiomyopathy(HCM)is very complicated,particularly regarding the role of circular RNA(circRNA).This research pays special attention to the relationships of the circRNA-mediated network,including RNA-RNA relationships and RNA-RNA binding protein(RNA-RBP)relationships.We use the parameter framework technology proposed in this paper to screen differentially expressed circRNA,messenger RNA(mRNA),and microRNA(miRNA)from the expression profile of samples related to HCM.And 31 pairs of circRNA and mRNA relationship pairs were extracted,combined with the miRNA targeting database;145 miRNA-mRNA relationship pairs were extracted;268 circRNA-mRNA-miRNA triads were established through the common mRNA in the 2 types of relationship pairs.Thus,268 circRNA-miRNA regulatory relationships were deduced and 30 circRNARBP relationship pairs were analyzed at the protein level.On this basis,a circRNA-mediated regulatory network corresponding to the two levels of RNA-RNA and RNA-RBP was established.And then the roles of circRNA in HCM were analyzed through circRNA-mRNA,circRNA-miRNA,and circRNA-RBP,and the possible role in disease development mas inferred.
基金supported by the Aeronautical Science Foundation of China under Grant No.20142080011
文摘The studies on clutter modeling and suppression of airborne radar with a parabolic conformal array are uncommon due to the complexity of this type of antenna array configuration.The correct understanding of clutter characteristics for airborne radar with a parabolic conformal antenna array is the prerequisite and foundation of optimal suppression of this type of clutter.This paper establishes the model of clutter echo of airborne parabolic conformal phased array radar and analyzes the structure characteristics and the distribution features of this type of clutter.The simulation results show that this type of clutter has the following characteristics:1) The main lobe on the azimuth is seriously broadened,2) the power spectrum presents strong heterogeneity,and 3) the freedom degrees are high.Based on the existing related clutter suppression methods,we verified the correctness of the constructed clutter model.This work has an important guidance to further study on clutter suppression methods in airborne parabolic conformal array radar.
基金the National Natural Science Foundation of China under Grants No.61872405 and No.61720106004the Key Project of Natural Science Foundation of Guangdong Province under Grant No.2016A030311040.
文摘The biological features of the valvular heart disease with atrial fibrillation(AF-VHD)remain unknown when involving long non-coding RNAs(lncRNAs).This study performed system analysis on lncRNA and messenger RNA(mRNA)expression profiles constructed by using bioinformatics methods and tools for biological features of AF-VHD.Fold change and t-test were used to identify differentially expressed(DE)lncRNAs and mRNAs.The enrichment analysis of DE mRNAs was performed.The subgroups formed by lncRNAs and nearby mRNAs were screened,and a transcriptional regulation network among lncRNAs,mRNAs,and transcription factors(TFs)was constructed.The interactions between mRNAs related to lncRNAs and drugs were predicted.The 620 AF-VHDrelated DE lncRNAs and 452 DE mRNAs were identified.The 3 lncRNA subgroups were screened.The 665 regulations mediated by lncRNAs and TFs were identified.The 9 mRNAs related to lncRNAs had 1 or more potential drug interactions,totaling 37 drugs.Of these,9 drugs targeting 3 genes are already known to be able to control or trigger atrial fibrillation(AF)or other cardiac arrhythmias.The found biological features of AF-VHD provide foundations for further biological experiments to better understand the roles of lncRNAs in development from the valvular heart disease(VHD)to AF-VHD.
基金supported by National Natural Science Foundation of China (Grant No. 51307135)China Postdoctoral Science Foundation (Grant No. 2017M610639)the Fundamental Research Funds for Central Universities
文摘Cold atmospheric-pressure plasma is a new technology, widely used in many fields of biomedicine,especially in cancer treatment. Cold plasma can selectively kill a variety of tumor cells, and its biological safety in clinical trials is also very important. In many cases, the patient's immune level is relatively low, so we first studied the safety assessment of plasma treatment in an immunocompromised animal model. In this study, we examined the safety of immuno-deficient nude mice by oral lavage treatment of plasma-activated water, and studied the growth status, main organs and blood biochemical indexes. Acute toxicity test results showed that the maximum dose of plasma treatment for 15 min had no lethal effect and other acute toxicity. There were no significant changes in body weight and survival status of mice after 2 min and 4 min of plasma-activated water(PAW)treatment for 2 weeks. After treatment, the major organs, including heart, liver, spleen, lung and kidney, were not significantly changed in organ coefficient and tissue structure. Blood biochemical markers showed that blood neutrophils and mononuclear cells were slightly increased, and the others remained unchanged. Liver function, renal function, electrolytes, glucose metabolism and lipid metabolism were not affected by different doses of PAW treatment. The above results indicate that PAW treatment can be used to treat immuno-deficient nude mice without significant safety problems.
基金supported by National Natural Science Foundation of China(Nos.12075188,52077166 and 51837008)State Key Laboratory of Electrical Insulation and Power Equipment(No.EIPE20302).
文摘In this study,we investigated the effects of the quartz tube diameter,air flow rate,and applied voltage on the characteristics of an air plasma jet to obtain the optimized discharge characteristics.The physicochemical properties and concentration of reactive oxygen and nitrogen species(RONS)in plasma-activated medium(PAM)were characterized to explore their chemical activity.Furthermore,we investigated the inactivation effect of air plasma jet on tumour cells and their corresponding inactivation mechanism.The results show that the tube diameter plays an important role in sustaining the voltage of the air plasma jet,and the gas flow rate affects the jet length and discharge intensity.Additionally,the air plasma jet discharge displays two modes,namely,ozone and nitrogen oxide modes at high and low gas flow rates,respectively.Increasing the voltage increases the concentration of reactive species and the length of discharge.By evaluating the viability of A549 cells under different parameters,the optimal treatment conditions were determined to be a quartz tube diameter of 4 mm,gas flow rate of 0.5 SLM,and voltage of 18 k V.Furthermore,an air plasma jet under the optimized conditions effectively enhanced the chemical activity in PAM and produced more aqueous RONS.The air plasma jet induced significant cytotoxicity in A549 cancer cells after plasma treatment.H_(2)O_(2) and NO_(2) are regarded as key factors in promoting cell inactivation.The present study demonstrates the potential use of tumour cell therapy by atmospheric air PAM,which aids a better understanding of plasma liquid chemistry.
文摘Objective: To analyze the non-periodic, unstable and even chaotic echoes scattered from microbubbles which are extremely sensitive and may easily collapse, fragment or shrink when ultrasound contrast agents are exposed to ultrasound (US) irradiation. Methods: The combined time-frequency analysis was applied to the original signals instead of the traditional Fourier spectral analysis technique. Results: The results obtained from simulation as well as experiment showed that the subharmonic, 2nd harmonic and ultra harmonic of the microbubbles occurred during the oscillation and varied with time. The dependence on the incident ultrasonic amplitude and microbubble parameters were established. Conclusion: The transient echoes backscattered from the ultrasound agent in the evaluation of the blood perfusion can be analyzed thoroughly by the technique of combined-frequency analysis and the time detail of the frequency contents can be revealed.
基金supported by the National Natural Science Foundation of China under Grant No.81171411the Key Technology Research and the Development Program of Sichuan Province under Grant No.2011FZ0034
文摘Genomic islands(Gis)are one of the most important components for cyanobacterial genome.The Gis code has many functions,such as symbiosis,pathogenesis,and adaptation.In this article,we predict and analyze the Gis in Synechocystis sp.PCC 6803 by bioinfomatics,and the results show that ISL1,ISL8,and ISL16 are homologous with many other bacteria,and they involve in basic reactions and have a conservative evolution.On the contrary,ISL15 has a unique sequence and function only for Synechocystis sp.PCC6803.Most of Gis play a role in genome rearrangement because they have lots of transposase.Moreover,we find that recombination and horizontal transfer of Gis are important factors to affect the distribution of non-coding RNA.Our work contributes to a comprehensive understanding of genomic islands and their impact on genome of cyanobacteria.
基金This work was supported by the National Natural Science Foundation of China(NSFC)(61773094,62076055,62106208)the Science and Technology Project of Sichuan Province,(2020JDRC0031)the China Postdoctoral Science Foundation(2021TQ0272,2021M702715).
文摘Dear Editor,Traffic driving is a dynamic and complicated task in which drivers are required to pay close attention to the important targets or regions to maintain safe margins.Rainy weather conditions make it more challenging with factors such as low visibility,raindrops,pedestrian with umbrellas,wipers,etc.Studies showed that rainy condition affects driving safety significantly[1],[2].It is reported that,in raining weather condition,the odds for a fatal accident are 3.340 times higher on highways than on streets[3].An investigation of the relationship between rainfall and fatal crashes in Texas from 1994 to 2018 on fatality analysis reporting system(FARS)database illustrated that rain-related fatal crashes represented about 6.8%of the total fatal crashes on average,moreover,the proportion showed high variability at the annual,monthly,and hourly time scales[4].Therefore,raining is a complex and critical factor for road safety planning and management.In fact,the traffic environment is a dynamic scene with multiple sources of information,including important targets that are highly relevant to the current driving task as well as irrelevant targets that may distract the driving task[5].
基金supported by the National Key R&D Program of China(Grant nos.2018YFC1311500(B.S.),2017YFC0907500(K.Y.)and 2018YFC0910400(K.Y.))National Science Foundation of China(NSFC)(Grant nos.81970679(B.S.),81500690(Y.W.),and 31671372(K.Y.))+3 种基金Natural Science Foundation of Shaanxi Province(2018JM70990(Y.W.))Key Research and Development Project of Shaanxi Province(Grant no.2017ZDXM-SF-060(B.S.))Fundamental Research Funds for the Central Universities(1191329875(Y.W.))the China Postdoctoral Science Foundation(224646(Y.W.)).
文摘Graves*orbitopathy(GO),the most severe manifestation of Graves'hyperthyroidism(GH),is an autoimmune-mediated inflammatory disorder,and treatments often exhibit a low efficacy.CD4+T cells have been reported to play vital roles in GO progression.To explore the pathogenic CD4-f T cell types that drive GO progression,we applied single-cell RNA sequencing(scRNA-Seq),T cell receptor sequencing(TCR-Seq),flow cytometry,immunofluorescence and mixed lymphocyte reaction(MLR)assays to evaluate CD4+T cells from GO and GH patients.scRNA-Seq revealed the novel GO-spedfic cell type CD4+cytotoxic T lymphocytes(CTLs),which are characterized by chemotactic and inflammatory features.The clonal expansion of this CD4+CTL population,as demonstrated by TCR-Seq,along with their strong cytotoxic response to autoantigens,localization in orbital sites,and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-y-secreting CD4+CTLs in GO.Therefore,cytotoxic pathways may become potential therapeutic targets for GO.
文摘The world has entered an era featured with fast transportations,instant communications,and prompt technological revolutions,the further advancement of which all relies fundamentally,yet,on the development of cost-effective energy resources allowing for durable and high-rate energy supply.Current battery and fuel cell systems are challenged by a few issues characterized either by insufficient energy capacity or by operation instability and,thus,are not ideal for such highly-demanded applications as electrical vehicles and portable electronic devices.In this mini-review,we present,from materials perspectives,a few selected important breakthroughs in energy resources employed in these applications.Prospectives are then given to look towards future research activities for seeking viable materials solutions for addressing the capacity,durability,and cost shortcomings associated with current battery/fuel cell devices.
基金supported by the National Key R&D Program of China(Grant Nos.2018YFC0910400 and2017YFC0907500)the National Natural Science Foundation of China(Grant Nos.31671372 and 31701739)
文摘Every human being looks different in one way or the other.That’s the work of genetic variations,the ultimate driving force for evolution as well as the cause for many human diseases.Mapping human genetic variants reveals global genetic diversity,and pinpoints causal variants behind genetic disorders.
基金supported by the National Key R&D Program of China(Grant Nos.2018YFC0910400 and 2017YFC0907500)the National Science Foundation of China(Grant Nos.31671372,61702406,and 31701739)+3 种基金the Fundamental Research Funds for the Central Universitiesthe World-Class Universities(Disciplines)the Characteristic Development Guidance Funds for the Central Universitiesthe Shanghai Municipal Science and Technology Major Project(Grant No.2017SHZDZX01)。
文摘Complex structural variants(CSVs) are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.However,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery compared with simple structural variants.Here,we systematically analyzed the multi-breakpoint connection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70%,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.