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Recurrent miscarriage (RM) affects millions of couples globally, and half of them have no demonstrated etiology. Genome sequencing (GS) is an enhanced and novel cytogenetic tool to define the contribution of chromosomal abnormalities in human diseases. In this study we evaluated its utility in RM-affected couples. We performed low-pass GS retrospectively for 1,090 RM-affected couples, all of whom had routine chromosome analysis. A customized sequencing and interpretation pipeline was developed to identify chromosomal rearrangements and deletions/duplications with confirmation by fluorescence in situ hybridization, chromosomal microarray analysis, and PCR studies. Low-pass GS yielded results in 1,077 of 1,090 couples (98.8%) and detected 127 chromosomal abnormalities in 11.7% (126/1,077) of couples; both members of one couple were identified with inversions. Of the 126 couples, 39.7% (50/126) had received former diagnostic results by karyotyping characteristic of normal human male or female karyotypes. Low-pass GS revealed additional chromosomal abnormalities in 50 (4.0%) couples, including eight with balanced translocations and 42 inversions. Follow-up studies of these couples showed a higher miscarriage/fetal-anomaly rate of 5/10 (50%) compared to 21/93 (22.6%) in couples with normal GS, resulting in a relative risk of 2.2 (95% confidence interval, 1.1 to 4.6). In these couples, this protocol significantly increased the diagnostic yield of chromosomal abnormalities per couple (11.7%) in comparison to chromosome analysis (8.0%, chi-square test p = 0.000751). In summary, low-pass GS identified underlying chromosomal aberrations in 1 in 9 RM-affected couples, enabling identification of a subgroup of couples with increased risk of subsequent miscarriage who would benefit from a personalized intervention.
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Aborto Habitual/diagnóstico , Aborto Habitual/genética , Aberraciones Cromosómicas , Secuenciación Completa del Genoma/métodos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Cariotipificación , Masculino , Embarazo , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. METHODS: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. FINDINGS: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. INTERPRETATION: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. FUNDING: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Genoma Viral , Neumonía Viral/epidemiología , Neumonía Viral/virología , Receptores Virales/metabolismo , Betacoronavirus/metabolismo , Líquido del Lavado Bronquioalveolar/virología , COVID-19 , China/epidemiología , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/transmisión , ADN Viral/genética , Reservorios de Enfermedades/virología , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Filogenia , Neumonía Viral/diagnóstico , Neumonía Viral/transmisión , SARS-CoV-2 , Alineación de SecuenciaRESUMEN
Image edge detection is a fundamental problem in image processing and computer vision, particularly in the area of feature extraction. However, the time complexity increases squarely with the increase of image resolution in conventional serial computing mode. This results in being unbearably time consuming when dealing with a large amount of image data. In this paper, a novel resolution free parallel implementation algorithm for gradient based edge detection, namely EDENP, is proposed. The key point of our method is the introduction of an enzymatic numerical P system (ENPS) to design the parallel computing algorithm for image processing for the first time. The proposed algorithm is based on a cell-like P system with a nested membrane structure containing four membranes. The start and stop of the system is controlled by the variables in the skin membrane. The calculation of edge detection is performed in the inner three membranes in a parallel way. The performance and efficiency of this algorithm are evaluated on the CUDA platform. The main advantage of EDENP is that the time complexity of O ( 1 ) can be achieved regardless of image resolution theoretically.
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Algoritmos , Modelos Teóricos , HumanosRESUMEN
PURPOSE: Recent studies demonstrate that whole-genome sequencing enables detection of cryptic rearrangements in apparently balanced chromosomal rearrangements (also known as balanced chromosomal abnormalities, BCAs) previously identified by conventional cytogenetic methods. We aimed to assess our analytical tool for detecting BCAs in the 1000 Genomes Project without knowing which bands were affected. METHODS: The 1000 Genomes Project provides an unprecedented integrated map of structural variants in phenotypically normal subjects, but there is no information on potential inclusion of subjects with apparent BCAs akin to those traditionally detected in diagnostic cytogenetics laboratories. We applied our analytical tool to 1,166 genomes from the 1000 Genomes Project with sufficient physical coverage (8.25-fold). RESULTS: With this approach, we detected four reciprocal balanced translocations and four inversions, ranging in size from 57.9 kb to 13.3 Mb, all of which were confirmed by cytogenetic methods and polymerase chain reaction studies. One of these DNAs has a subtle translocation that is not readily identified by chromosome analysis because of the similarity of the banding patterns and size of exchanged segments, and another results in disruption of all transcripts of an OMIM gene. CONCLUSION: Our study demonstrates the extension of utilizing low-pass whole-genome sequencing for unbiased detection of BCAs including translocations and inversions previously unknown in the 1000 Genomes Project.
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Trastornos de los Cromosomas/diagnóstico , Análisis Citogenético/métodos , Aberraciones Cromosómicas , Inversión Cromosómica/genética , Cromosomas/genética , Reordenamiento Génico/genética , Genoma/genética , Proyecto Genoma Humano , Humanos , Cariotipificación/métodos , Translocación Genética/genética , Secuenciación Completa del Genoma/métodosRESUMEN
In this paper, we propose a reflective long-period grating-based sensor with a Sagnac fiber loop mirror (SFLM) for simultaneous measurement of refractive index (RI) and temperature. By cascading the SFLM to the end of a long-period fiber grating (LPFG), the LPFG works as a reflection operation, which is convenient in some applications. Further, the SFLM and the LPFG have different sensitivities to RI and temperature. As a result, RI and temperature measurement can be simultaneously achieved by monitoring the wavelength shifts of the LPFG and the SFLM's dips in the reflection spectrum. Experimental results show that the temperature sensitivity can reach 1.533 nm/°C, and the RI sensitivity is from 16.864 nm/RIU (refractive index unit) to 113.142 nm/RIU when the RI range is from 1.333 to 1.430. The application for 40 km long-distance RI and temperature measurement shows that the sensor has potential application in long-distance sensing.
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Tecnología de Fibra Óptica/instrumentación , Interferometría/instrumentación , Lentes , Fotometría/instrumentación , Refractometría/instrumentación , Termografía/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , TemperaturaRESUMEN
3D (three-dimensional) structured light scanning system is widely used in the field of reverse engineering, quality inspection, and so forth. Camera calibration is the key for scanning precision. Currently, 2D (two-dimensional) or 3D fine processed calibration reference object is usually applied for high calibration precision, which is difficult to operate and the cost is high. In this paper, a novel calibration method is proposed with a scale bar and some artificial coded targets placed randomly in the measuring volume. The principle of the proposed method is based on hierarchical self-calibration and bundle adjustment. We get initial intrinsic parameters from images. Initial extrinsic parameters in projective space are estimated with the method of factorization and then upgraded to Euclidean space with orthogonality of rotation matrix and rank 3 of the absolute quadric as constraint. Last, all camera parameters are refined through bundle adjustment. Real experiments show that the proposed method is robust, and has the same precision level as the result using delicate artificial reference object, but the hardware cost is very low compared with the current calibration method used in 3D structured light scanning system.
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Algoritmos , Modelos Teóricos , CalibraciónRESUMEN
Metagenomic next-generation sequencing (mNGS) provides considerable advantages in identifying emerging and re-emerging, difficult-to-detect and co-infected pathogens; however, the clinical application of mNGS remains limited primarily due to the lack of quantitative capabilities. This study introduces a novel approach, KingCreate-Quantification (KCQ) system, for quantitative analysis of microbes in clinical specimens by mNGS, which co-sequence the target DNA extracted from the specimens along with a set of synthetic dsDNA molecules used as Internal-Standard (IS). The assay facilitates the conversion of microbial reads into their copy numbers based on IS reads utilizing a mathematical model proposed in this study. The performance of KCQ was systemically evaluated using commercial mock microbes with varying IS input amounts, different proportions of human genomic DNA, and at varying amounts of sequence analysis data. Subsequently, KCQ was applied in microbial quantitation in 36 clinical specimens including blood, bronchoalveolar lavage fluid, cerebrospinal fluid and oropharyngeal swabs. A total of 477 microbe genetic fragments were screened using the bioinformatic system. Of these 83 fragments were quantitatively compared with digital droplet PCR (ddPCR), revealing a correlation coefficient of 0.97 between the quantitative results of KCQ and ddPCR. Our study demonstrated that KCQ presents a practical approach for the quantitative analysis of microbes by mNGS in clinical samples.
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Ácidos Nucleicos , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento , Líquido del Lavado Bronquioalveolar , Biología Computacional , ADNRESUMEN
Background: A rapid and precise etiological diagnosis is crucial for the effective treatment of bloodstream infection (BSI). In this study, the performance of probe capture-based targeted next-generation sequencing (tNGS) was compared to that of blood culture and metagenomic next-generation sequencing (mNGS) in detecting potential pathogens in patients with BSI. Methods: A total of 80 patients with suspected BSI were prospectively enrolled from 24 November 2023 to 30 December 2023 at Zhongshan Hospital, Shanghai, China. All 80 participants underwent simultaneous blood culture, blood mNGS, and blood tNGS after admission when febrile, and the results were compared. Results: Among the 80 participants, 11 were clinically diagnosed with noninfectious fever, and 69 were diagnosed with BSI. Blood tNGS had a higher sensitivity for the diagnosis of BSI than blood culture (91.3% vs. 23.2%, P<0.001) and blood mNGS (91.3% vs. 69.6%, P=0.001). There was no significant difference in specificity between blood mNGS and tNGS (81.8% vs. 100.0%, P=0.13). Blood tNGS demonstrated a faster turnaround time than blood culture and blood mNGS. In 22 (31.9%) patients with BSI, targeted adjustment of the anti-infectious therapy according to the blood tNGS results resulted in clinical improvement. Conclusions: Blood tNGS may be a promising tool for detecting potential pathogens in patients with BSI. The application of blood tNGS for BSI could guide anti-infectious treatment strategies and might improve clinical outcomes.
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MOTIVATION: The boost of next-generation sequencing technologies provides us with an unprecedented opportunity for elucidating genetic mysteries, yet the short-read length hinders us from better assembling the genome from scratch. New protocols now exist that can generate overlapping pair-end reads. By joining the 3' ends of each read pair, one is able to construct longer reads for assembling. However, effectively joining two overlapped pair-end reads remains a challenging task. RESULT: In this article, we present an efficient tool called Connecting Overlapped Pair-End (COPE) reads, to connect overlapping pair-end reads using k-mer frequencies. We evaluated our tool on 30× simulated pair-end reads from Arabidopsis thaliana with 1% base error. COPE connected over 99% of reads with 98.8% accuracy, which is, respectively, 10 and 2% higher than the recently published tool FLASH. When COPE is applied to real reads for genome assembly, the resulting contigs are found to have fewer errors and give a 14-fold improvement in the N50 measurement when compared with the contigs produced using unconnected reads. AVAILABILITY AND IMPLEMENTATION: COPE is implemented in C++ and is freely available as open-source code at ftp://ftp.genomics.org.cn/pub/cope. CONTACT: twlam@cs.hku.hk or luoruibang@genomics.org.cn
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Algoritmos , Arabidopsis/genética , Mapeo Cromosómico , Genómica/métodos , Análisis de Secuencia de ADN/métodos , Mapeo ContigRESUMEN
MOTIVATION: The next-generation high-throughput sequencing technologies, especially from Illumina, have been widely used in re-sequencing and de novo assembly studies. However, there is no existing software that can simulate Illumina reads with real error and quality distributions and coverage bias yet, which is very useful in relevant software development and study designing of sequencing projects. RESULTS: We provide a software package, pIRS (profile-based Illumina pair-end reads simulator), which simulates Illumina reads with empirical Base-Calling and GC%-depth profiles trained from real re-sequencing data. The error and quality distributions as well as coverage bias patterns of simulated reads using pIRS fit the properties of real sequencing data better than existing simulators. In addition, pIRS also comes with a tool to simulate the heterozygous diploid genomes. AVAILABILITY: pIRS is written in C++ and Perl, and is freely available at ftp://ftp.genomics.org.cn/pub/pIRS/.
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Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Análisis de Secuencia de ADN/métodos , Programas Informáticos , Simulación por Computador , Proyecto Genoma Humano , Humanos , Cadenas de MarkovRESUMEN
As a core step of obstacle avoidance and path planning, dynamic obstacle detection is critical for autonomous driving. This study aimed to propose a dynamic obstacle detection method based on U-V disparity and residual optical flow for autonomous driving. First, a drivable area of an unmanned vehicle was detected using U-V disparity images. Then, obstacles in the drivable area were detected using U-V disparity images and the geometric relationship between obstacle size and its disparity. Finally, the motion likelihood of each obstacle was estimated by compensating the camera ego-motion. The innovation of the proposed method was that the searching range of the moving obstacles was greatly narrowed by detecting the obstacles in the drivable area, which greatly improved not only the moving obstacle detection efficiency but also the detection accuracy. Datasets from the KITTI benchmark and our self-acquired campus scene data were chosen as testing samples. The experimental results showed that our method could achieve high detection precision, low missed detection rate and less time consumption.
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AIM OF THE STUDY: To evaluate the clinical efficacy and safety of commonly used oral Chinese patent medicines for the treatment of coronary heart disease combined with hyperlipidemia in clinical practice through a network meta-analysis. MATERIALS AND METHODS: PubMed, Embase, Cochrane Library, Web of Science, Wanfang, VIP, SinoMed, and CNKI databases were searched for all published randomized controlled trials (RCTs) on the treatment of coronary heart disease combined with hyperlipidemia using Chinese patent medicines. NoteExpress software was used to screen the literature obtained from the databases according to the inclusion and exclusion criteria. The Cochrane risk of bias assessment tool was used to evaluate the quality of the included studies. A network meta-analysis was performed using R 4.2.1. Subgroup analyses of outcome indicators were made based on conventional treatment (CT) methods. The incidence of adverse events in the included RCTs was statistically analyzed. A funnel plot was drawn using RevMan 5.4.1 software for the assessment of bias in the total clinical effectiveness rate. Finally, the quality of evidence for interventions with statistically significant differences was evaluated using the GRADE system. RESULTS: A total of 78 RCTs were included, involving 7,955 cases and 8 types of Chinese patent medicines, which were Tongxinluo Capsule, Naoxintong Capsule, Compound Danshen Dripping Pill, Shexiangbaoxin Pill, Songling Xuemaikang Capsule, Xuezhikang Capsule, Yindan Xinnaotong Capsule, and Zhibitai Capsule. A total of 24 RCTs reported the incidence of adverse events, but no statistically significant difference in the incidence of adverse events was found between the experimental and control groups in each study (P > 0.05). There was no obvious publication bias in all studies, but the overall quality of evidence in the included RCTs was low. Comparison of different intervention measures showed that Naoxintong Capsule + CT improved the cardiac index and cardiac output, and lowered the low-density lipoprotein cholesterol and total cholesterol levels. Tongxinluo Capsule + CT raised high-density lipoprotein cholesterol levels and reduced triglyceride levels. Xuezhikang Capsule + CT improved the total clinical effectiveness rate. Subgroup analyses showed that differences in CT did not cause heterogeneity in the results. CONCLUSION: Compared with the use of CT alone, the combined use of Chinese patent medicines with CT can effectively improve the symptoms in patients with both coronary heart disease and hyperlipidemia.
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Background: Deep learning-based magnetic resonance imaging (MRI) methods require in most cases a separate dataset with thousands of images for each anatomical site to train the network model. This paper proposes a miniature U-net method for k-space-based parallel MRI where the network model is trained individually for each scan using scan-specific autocalibrating signal data. Methods: The original U-net was tailored with fewer layers and channels, and the network was trained using the autocalibrating signal data with a mixing loss function involving magnitude loss and phase loss. The performance of the proposed method was measured using both phantom and in vivo datasets compared to scan-specific robust artificial-neural-networks for k-space interpolation (RAKI) and generalized autocalibrating partially parallel acquisitions (GRAPPA). Results: The proposed method alleviates aliasing artifacts and reduces noise with an acceleration factor of four for phantom and in vivo data. Compared with RAKI and GRAPPA, the proposed method represents an improvement with a structural similarity index measure of between 0.02 and 0.05 and a peak signal-to-noise ratio (PSNR) of between 0.1 and 3. Conclusions: The proposed method introduces a miniature U-net to reconstruct the missing k-space data, which can provide an optimal trade-off between network performance and requirement of training samples. Experimental results indicate that the proposed method can improve image quality compared with the deep learning-based k-space parallel magnitude resonance imaging method.
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Purpose: Angiogenesis post-ischemia plays an essential role in preventing ischemic damage to tissue by improving the blood recovery. Determining the regulatory mechanism of ischemic angiogenesis, therefore, could provide effective therapeutics for ischemic injury. Materials and Methods: The RNA sequencing (RNA-seq) database was used to predict the association of gamma-aminobutyric acid type B receptor subunit 2 (GABBR2) with endothelial-specific expression. The role of GABBR2 in angiogenesis was verified in vitro by downregulating GABBR2 in human umbilical vein endothelial cells (HUVECs) with lentiviral vectors. Besides, the in vivo effect of GABBR2 on the blood recovery of an ischemic hindlimb was demonstrated by establishing a hindlimb ischemia model in normal and GABBR2 adenoviral vector-infected mice. Then, the mobilization of endothelial progenitor cells (EPCs) in peripheral blood post-ischemia was determined by flow cytometry. Finally, the XF analyzer and Western blot were used to determine the effect of GABBR2 on endothelial metabolism. Results: The RNA-seq results indicated a strong association between GABBR2 and endothelial revascularization, and the upregulation of GABBR2 was detected in both hypoxia-treated HUVECs and ischemic mouse hindlimb. Hypoxia treatment for 6 h increased the proliferation, migration, and tube formation of HUVECs, which were inhibited by GABBR2 knockdown. Additionally, GABBR2 downregulation significantly decreased the blood flow recovery of mouse ischemic hindlimb. The expressions of the EPC markers CD34+ and CD133+ significantly decreased in the peripheral blood in hindlimb post-ischemia. Mechanically, glycolysis-dominated metabolism of HUVECs was compromised by GABBR2 knockdown. Evidences of the decreased expressions of HKII, PFKFB3, and PKM1 also supported the compromised glycolysis induced by GABBR2 downregulation. Conclusion: Our study demonstrated that GABBR2 regulated angiogenesis post-ischemia by inhibiting the glycolysis pathway.
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BACKGROUND: In COVID-19 patients, information regarding superinfection, antimicrobial assessment, and the value of metagenomic sequencing (MS) could help develop antimicrobial stewardship. METHOD: This retrospective study analyzed 323 laboratory-confirmed COVID-19 patients for co-infection rate and antimicrobial usage in the Shanghai Public Health Clinical Center (SPHCC) from January 23rd to March 14th 2020. The microbiota composition was also investigated in patients with critically severe COVID-19. RESULTS: The total population co-infection rate was 17/323 (5.3%) and 0/229 (0), 4/78 (5.1%), and 13/16 (81.3%) for the mild, severe, and critically severe subgroups, respectively. Proven fungal infection was significantly associated with a higher mortality rate (p = 0.029). In critically severe patients, the rate of antimicrobials and carbapenem usage were 16/16 (100%) and 13/16 (81.3%), respectively, in which the preemptive and empiric antimicrobial days accounted for 51.6% and 30.1%, respectively. Targeted therapy only accounted for 18.3%. MS was implemented to detect non-COVID-19 virus co-existence and the semi-quantitative surveillance of bacteremia, with clear clinical benefit seen in cases with MS-based precision antimicrobial management. Airway microbiome analysis suggested that the microbiota compositions in critically severe COVID-19 patients were likely due to intubation and mechanical ventilation. CONCLUSIONS: In the SPHCC cohort, we observed a non-negligible rate of super-infection, especially for the critically ill COVID-19 patients. Fungal co-infection requires intensive attention due to the high risk of mortality, and the clinical benefit of MS in guiding antimicrobial management warrants further investigation.
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Antibacterianos/uso terapéutico , COVID-19 , Metagenómica , Microbiota/fisiología , Sistema Respiratorio/microbiología , Sobreinfección/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Programas de Optimización del Uso de los Antimicrobianos , China , Estudios de Cohortes , Coinfección/tratamiento farmacológico , Enfermedad Crítica , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Microbiota/genética , Persona de Mediana Edad , Micosis/tratamiento farmacológico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVES: Current evidence suggests that microorganisms are associated with neoplastic diseases; however, the role of the airway microbiome in lung cancer remains unknown. To investigate the taxonomic profiles of the lower respiratory tract (LRT) microbiome in patients with lung cancer. MATERIALS AND METHODS: BALF samples were collected in a discovery set comprising 150 individuals, including 91 patients with lung cancer, 29 patients with nonmalignant pulmonary diseases and 30 healthy subjects, and an independent validation set including 85 participants. The samples were assessed by metagenomics analysis. Random forest regression analysis was performed to select a diagnostic panel. RESULTS: In the discovery set, richness was reduced in lung cancer patients compared with that in healthy subjects, and the microbiome of patients with nonmalignant diseases resembled that of patients with lung cancer. Interestingly, Bradyrhizobium japonicum was only found in patients with lung cancer, whereas Acidovorax was found in patients with cancer and nonmalignant pulmonary diseases. A microbiota-related diagnostic model consisting of age, pack year of smoking and eleven types of bacteria was built, and the area under the curve (AUC) for discriminating the patients with cancer was 0.882 (95%CI: 0.807-0.957) in the training set and 0.796 (95%CI: 0.673-0.920) in the independent validation set. CONCLUSION: Our study demonstrates that the LRT microbiome richness is diminished in lung cancer patients compared with that in healthy subjects and that microbiota-specific biomarkers may be useful for diagnosing patients for whom lung biopsy is not feasible.
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Biodiversidad , Neoplasias Pulmonares/complicaciones , Microbiota , Infecciones del Sistema Respiratorio/etiología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Biomarcadores , Femenino , Perfilación de la Expresión Génica , Humanos , Masculino , Metagenoma , Metagenómica/métodos , Persona de Mediana Edad , Estadificación de Neoplasias , Infecciones del Sistema Respiratorio/diagnósticoRESUMEN
Balanced chromosomal rearrangements (or balanced chromosome abnormalities, BCAs) are common chromosomal structural variants. Emerging studies have demonstrated the feasibility of using whole-genome sequencing (WGS) for detection of BCA-associated breakpoints, but the requirement for a priori knowledge of the rearranged regions from G-banded chromosome analysis limits its application. The protocols described here are based on low-pass WGS for detecting BCA events independent from chromosome analysis, and has been validated using genomic data from the 1000 Genomes Project. This approach adopts non-size-selected mate-pair library (3â¼8 kb) with 2â¼3 µg DNA as input, and requires only 30 million read-pairs (50 bp, equivalent to 1-fold base-coverage) for each sample. The complete procedure takes 13 days and the total cost is estimated to be less than $600 (USD) per sample. © 2018 by John Wiley & Sons, Inc.
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Aberraciones Cromosómicas , Trastornos de los Cromosomas/genética , Genoma Humano/genética , Secuenciación Completa del Genoma , Trastornos de los Cromosomas/patología , Mapeo Cromosómico , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Translocación GenéticaRESUMEN
BACKGROUND: We investigated a large family with Pierre Robin sequence (PRS). AIM OF THE STUDY: This study aims to determine the genetic cause of PRS. RESULTS: The reciprocal translocation t(4;6)(q22;p21) was identified to be segregated with PRS in a three-generation family. Whole-genome sequencing and Sanger sequencing successfully detected breakpoints in the intragenic regions of BMRP1B and GRM4. We hypothesized that PRS in this family was caused by (i) haploinsufficiency for BMPR1B or (ii) a gain of function mechanism mediated by the BMPR1B-GRM4 fusion gene. In an unrelated family, we identified another BMPR1B-splicing mutation that co-segregated with PRS. CONCLUSION: We detected two BMPR1B mutations in two unrelated PRS families, suggesting that BMPR1B disruption is probably a cause of human PRS. METHODS: GTG banding, comparative genomic hybridization, whole-genome sequencing, and Sanger sequencing were performed to identify the gene causing PRS.
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Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Mutación , Síndrome de Pierre Robin/genética , Adolescente , Adulto , Receptores de Proteínas Morfogenéticas Óseas de Tipo 1/metabolismo , Niño , Preescolar , Hibridación Genómica Comparativa , Femenino , Genotipo , Humanos , Lactante , Cariotipo , Masculino , Persona de Mediana Edad , Linaje , Fenotipo , Síndrome de Pierre Robin/diagnóstico , Síndrome de Pierre Robin/metabolismo , Translocación Genética , Secuenciación Completa del Genoma , Adulto JovenRESUMEN
[This corrects the article DOI: 10.1186/2047-217X-1-18.].
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Since the completion of the cucumber and panda genome projects using Illumina sequencing in 2009, the global scientific community has had to pay much more attention to this new cost-effective approach to generate the draft sequence of large genomes. To allow new users to more easily understand the assembly algorithms and the optimum software packages for their projects, we make a detailed comparison of the two major classes of assembly algorithms: overlap-layout-consensus and de-bruijn-graph, from how they match the Lander-Waterman model, to the required sequencing depth and reads length. We also discuss the computational efficiency of each class of algorithm, the influence of repeats and heterozygosity and points of note in the subsequent scaffold linkage and gap closure steps. We hope this review can help further promote the application of second-generation de novo sequencing, as well as aid the future development of assembly algorithms.