组学时代下机器学习方法在临床决策支持中的应用

随着组学技术的不断发展,对于不同层次和类型的生物数据的获取方法日益成熟。在疾病诊治过程中会产生大量数据,通过机器学习等人工智能方法解析复杂、多维、多尺度的疾病大数据,构建临床决策支持工具,辅助医生寻找快速且有效的疾病诊疗方案是非常必要的。在此过程中,机器学习等人工智能方法的选择显得尤为重要。基于此,本文首先从类型和算法角度对临床决策支持领域中常用的机器学习等方法进行简要综述,分别介绍了支持向量机、逻辑回归、聚类算法、Bagging、随机森林和深度学习,对机器学习等方法在临床决策支持中的应用做了相应总结和分类,并对它们的优势和不足分别进行讨论和阐述,为临床决策支持中机器学习等人工智能方法的选择提供有效参考。

Performance of common buckwheat(Fagopyrum esculentum M.) supplied with selenite or selenate for selenium biofortification in northeastern China

Selenium(Se)deficiency commonly occurs in soils of northeastern China and leads to insufficient Se intake by humans.A two-year field study of Se biofortification of common buckwheat supplied with 40 g Se ha^(-1)as selenite(Se(IV)),selenate(Se(VI)),or a combination(1/2 Se(IV+VI))was performed to investigate Se accumulation and translocation in plants and determine the effects of different forms of Se on the grain yield,biomass production,and Se use efficiency of plants and seeds.Se application increased seed Se concentrations to 47.1–265.1μg kg^(-1).Seed Se concentrations following Se(VI)or 1/2 Se(IV+VI)treatment exceeded 100μg kg^(-1),an amount suitable for crop Se biofortification.Se concentration in shoots and roots decreased with plant development,and Se translocation from root to shoot in Se(IV)-treated plants was lower than that in plants treated with 1/2 Se(IV+VI)and Se(VI).Both grain yield and biomass production increased under 1/2 Se(IV+VI)treatment,with grain yields reaching 1663.8 and 1558.5 kg ha^(-1)in 2015 and 2016,respectively,reflecting increases of 11.0% and 10.3% over those without Se application.The Se use efficiency of seeds and plants under Se(VI)treatment was significantly higher than those under 1/2 Se(IV+VI)and Se(IV)treatments.Thus,application of selenate could result in higher Se accumulation in buckwheat seeds than application of the other Se sources,but the combined application of selenate and selenite might be an alternative approach for improving buckwheat grain yield by Se biofortification in northeastern China.

基于微胶囊化聚磷酸铵和微胶囊化膨胀石墨的阻燃硬质聚氨酯泡沫复合材料的制备及性能

采用原位聚合法,以聚氨酯为壳材,制备微胶囊化聚磷酸铵(PUAPP)和微胶囊化膨胀石墨(PUEG)。采用XPS、FTIR、TG和SEM分别对PUAPP和PUEG进行表征,结果表明,聚氨酯有效包覆在聚磷酸铵和膨胀石墨表面,成功制备了PUAPP和PUEG。在此基础上,采用一步法全水发泡工艺将PUAPP和PUEG引入到聚氨酯硬泡(RPUF)中,制备出一系列阻燃RPUF复合材料。采用极限氧指数(LOI)、垂直燃烧(UL-94)、TG、万能试验机、导热及密度测试研究了PUAPP/RPUF、PUEG/RPUF及PUAPP-PUEG/RPUF复合材料的阻燃性能、力学性能、保温性能及热稳定性。研究表明,微胶囊化阻燃剂的加入可以提高RPUF复合材料的高温稳定性,PUEG/RPUF、PUAPP/RPUF和PUAPP-PUEG/RPUF复合材料在700℃的残炭率从1.2wt%分别提高至6.9wt%、11.2wt%和10.7wt%。阻燃测试表明,PUAPP和PUEG可以有效提高RPUF复合材料的阻燃性能,当加入10.4wt%PUAPP时,PUAPP/RPUF复合材料的LOI提高到22.3vol%,UL-94等级为V-0级;当加入10.4wt%PUEG时,PUEG/RPUF复合材料的LOI达到25.3vol%,UL-94等级为V-0级;PUAPP-PUEG/RPUF复合材料的LOI达到24.3vol%,UL-94等级为V-0级。SEM和拉曼测试表明,PUAPP和PUEG可以提高RPUF复合材料的炭渣石墨化程度,使炭渣的致密性更强。

GSA:Genome Sequence Archive

With the rapid development of sequencing technologies towards higher throughput and lower cost, sequence data are generated at an unprecedentedly explosive rate. To provide an efficient and easy-to-use platform for managing huge sequence data, here we present Genome Sequence Archive （GSA; http：//bigd.big.ac.cn/gsa or http：//gsa.big.ac.cn）, a data repository for archiving raw sequence data. In compliance with data standards and structures of the International Nucleotide Sequence Database Collaboration （INSDC）, GSA adopts four data objects （BioProject, BioSample, Experiment, and Run） for data organization, accepts raw sequence reads produced by a variety of sequencing platforms, stores both sequence reads and metadata submitted from all over the world, and makes all these data publicly available to worldwide scientific communities. In the era of big data, GSA is not only an important complement to existing INSDC members by alleviating the increasing burdens of handling sequence data deluge, but also takes the significant responsibility for global big data archive and provides free unrestricted access to all publicly available data in support of research activities throughout the world.

Whole Genome Analyses of Chinese Population and De Novo Assembly of A Northern Han Genome

To unravel the genetic mechanisms of disease and physiological traits,it requires comprehensive sequencing analysis of large sample size in Chinese populations.Here,we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative(CASPMI)project launched by the Chinese Academy of Sciences,including the de novo assembly of a northern Han reference genome(NH1.0)and whole genome analyses of 597 healthy people coming from most areas in China.Given the two existing reference genomes for Han Chinese(YH and HX1)were both from the south,we constructed NH1.0,a new reference genome from a northern individual,by combining the sequencing strategies of PacBio,10×Genomics,and Bionano mapping.Using this integrated approach,we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1.In order to generate a genomic variation map of Chinese populations,we performed the whole-genome sequencing of 597 participants and identified 24.85 million(M)single nucleotide variants(SNVs),3.85 M small indels,and 106,382 structural variations.In the association analysis with collected phenotypes,we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males.Moreover,significant genetic diversity in MTHFR,TCN2,FADS1,and FADS2,which associate with circulating folate,vitamin B12,or lipid metabolism,was observed between northerners and southerners.Especially,for the homocysteine-increasing allele of rs1801133(MTHFR 677T),we hypothesize that there exists a “comfort”zone for a high frequency of 677T between latitudes of 35–45 degree North.Taken together,our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Characterization of miRNomes in Acute and Chronic Myeloid Leukemia Cell Lines

Myeloid leukemias are highly diverse diseases and have been shown to be associated with microRNA（miRNA） expression aberrations. The present study involved an in-depth miRNome analysis of two human acute myeloid leukemia（AML） cell lines, HL-60 and THP-1, and one human chronic myeloid leukemia（CML） cell line, K562, via massively parallel signature sequencing. mRNA expression profiles of these cell lines that were established previously in our lab facilitated an integrative analysis of miRNA and mRNA expression patterns. miRNA expression profiling followed by differential expression analysis and target prediction suggested numerous miRNA signatures in AML and CML cell lines. Some miRNAs may act as either tumor suppressors or oncomiRs in AML and CML by targeting key genes in AML and CML pathways. Expression patterns of cell type-specific miRNAs could partially reflect the characteristics of K562, HL-60 and THP-1 cell lines, such as actin filament-based processes, responsiveness to stimulus and phagocytic activity. miRNAs may also regulate myeloid differentiation, since they usually suppress differentiation regulators. Our study provides a resource to further investigate the employment of miRNAs in human leukemia subtyping, leukemogenesis and myeloid development. In addition, the distinctive miRNA signatures may be potential candidates for the clinical diagnosis, prognosis and treatment of myeloid leukemias.

CH_4 and N_2O emissions from double-rice cropping system as affected by Chinese milk vetch and straw incorporation in southern China

Chinese milk vetch(CMV) and rice straw(RS)were incorporated into soil to substitute for synthetic N fertilizers and to maintain soil fertility. However, little is known about the integrated impacts of CMV and RS incorporation on CH_4 and N_2O emissions in double-rice cropping systems in southern China. A field experiment was conducted to estimate the integrated impacts of CMV and RS incorporation in the early-and late-rice seasons on CH_4 and N_2O emissions. All treatments received uniform N inputs, 6%–37% of which was replaced by CMV and RS crop residue. CMV and/or RS incorporation produced equivalent or slightly more grain yield, while reducing N2 O emissions by 3%–43%. However, both CMV and RS incorporation increased CH_4 emissions. Annual CH_4 emissions ranged from 321 to 614 kg·hm^(–2)from CMV and RS amendment treatments, which were 1.5–2.9 times higher than that from synthetic N. Compared with single synthetic N fertilizer, incorporation of CMV and/or RS increased GWP and yield-scaled GWP by 45%–164% and45%–153%, respectively. Our results demonstrate CMV and RS amendments replacing N fertilizer, maintained stable yield, mitigated N_2O emission, but enhanced CH_4 emission. Further study is needed on crop residue management in double-cropping rice systems.

An RNA-seq-based Gene Expression Profiling of Radiation-induced Tumorigenic Mammary Epithelial Cells

Immortality and tumorigenicity are two distinct characteristics of cancers. Immortalization has been suggested to precede tumorigenesis. To understand the molecular mechanisms of tumorigenicity and cancer progression in mammary epithelium, we established a tumori- genic cell model by means of heavy-ion radiation of an immortal cell model, which was created by overexpressing the human telomerase reverse transcriptase （hTERT） in normal human mammary epithelial cells. We examined the expression profile of this tumorigenic cell line （T hMEC） using the hTERT-overexpressing immortal cell line （IhMEC） as a control. In-depth RNA-seq data was generated by using the next-generation sequencing （NGS） platform （Life Technologies SOLID3）. We found that house-keeping （HK） and tissue-spe- cific （TS） genes were differentially regulated during the tumorigenic process. HK genes tended to be activated while TS genes tended to be repressed. In addition, the HK genes and TS genes tended to contribute differentially to the variation of gene expression at different RPKM （gene expression in reads per exon kilobase per million mapped sequence reads） levels. Based on transcriptome analysis of the two cell lines, we defined 7053 differentially-expressed genes （DEGs） between immortality and tumorigenicity. Differential expression of 20 manually-selected genes was further validated using qRT-PCR. Our observations may help to further our understanding of cellular mechanism（s） in the transition from immortalization to tumorigenesis.

The diazotrophic community in oat rhizosphere: effects of legume intercropping and crop growth stage

In this study, the abundance, diversity and structure of the diazotrophic community in oat rhizosphere soil in three cropping systems and at two oat growth stages were investigated using real-time PCR and Illumina MiSeq sequencing. The nifH gene abundance in oat-soybean intercropping (OSO) and oat-mungbean intercropping (OMO) was significantly greater than that in sole oat (O), but the nifH gene abundance significantly decreased at the later stage in all the treatments. Alpha diversity indices in OSO and OMO were higher at the heading stage, but lower at the maturity stage than that in O. Bradyrhizobium and Skermanella were the dominant genera identified in all samples, with an average proportion of 35.8% and 12.4%, respectively. The proportion of dominant genera showed significant differences and varied with cropping system and growth stage. Principal component analysis showed that growth stage had a stronger effect than intercropping on the diazotrophic community structure. However, Mantel test and redundancy analysis showed there was no environmental factor significantly correlated to the diazotrophic community structure. Our results demonstrate that intercropping had a weaker effect than growth stage on the abundance, diversity and structure of the diazotrophic community in oat rhizosphere soil.

Effects of red and blue LEDs on in vitro growth and microtuberization of potato single-node cuttings

The objectives of this study were to investigate the effects of red and blue LEDs on in vitro growth and microtuberization of potato(Solanum tuberosum) singlenode cuttings. Explants were incubated under 6 light treatments: 100% red LEDs(R), 75% red LEDs + 25%blue LEDs(3 RB), 50% red LEDs + 50% blue LEDs(RB),25% red LEDs + 75% blue LEDs(R3 B), 100% blue LEDs(B) and white LEDs(W). Most of the growth and physiological parameters were significantly higher in3 RB than W. Enhancement of leaf area and chlorophyll concentrations were obtained in B. Leaf stomata were elliptical with the lowest density in 3 RB. However, those in W were round in shape, and those with the smallest size and the highest density were observed in R. Most of the characteristics of microtuberization were also improved in3 RB. The combined spectra of red and blue LEDs increased the number of large microtubers. The fresh weight of individual microtubers in R and W were increased, but not their number. These results suggest that, of the treatments assessed, 3 RB is optimal for the in vitro growth of potato plantlets and the combination of red and blue LEDs is beneficial for microtuberization.

Self-extinguishing and transparent epoxy resin modified by a phosphine oxide-containing bio-based derivative

A phosphine oxide-containing bio-based curing agent was synthesized by addition reaction between furan derivatives and diphenylphosphine oxide.The molecular structure of the as-prepared bio-based curing agent was confirmed by Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy.Dynamic mechanical analysis results indicated that with the increase of bio-based curing agent content,the glass transition temperature of epoxy/bio-based curing agent composites decreased,which was related to the steric effect of diphenylphosphine oxide species that possibly hinder the curing reaction as well as the reduction in the cross-linking density by mono-functional N-H.By the addition of 7.5 wt-%bio-based curing agent,the resulting epoxy composite achieved UL-94 V-0 rating,in addition to limiting oxygen index of 32.0 vol-%.With the increase of content for the bio-based curing agent,the peak of heat release rate and total heat release of the composites gradually decreased.The bio-based curing agent promoted the carbonization of the epoxy matrix,leading to higher char yield with good thermal resistance.The high-quality char layer served as an effective barrier to retard the diffusion of decomposition volatiles and oxygen between molten polymers and the flame.This study provides a renewable strategy for fabricating flame retardant and transparent epoxy thermoset.

Databases and Web Tools for Cancer Genomics Study

Publicly-accessible resources have promoted the advance of scientific discovery. The era of genomics and big data has brought the need for collaboration and data sharing in order to make effective use of this new knowledge. Here, we describe the web resources for cancer genomics research and rate them on the basis of the diversity of cancer types, sample size, omics data comprehensiveness, and user experience. The resources reviewed include data repository and analysis tools; and we hope such introduction will promote the awareness and facilitate the usage of these resources in the cancer research community.

GliomaDB: A Web Server for Integrating Glioma Omics Data and Interactive Analysis

Gliomas are one of the most common types of brain cancers.Numerous efforts have been devoted to studying the mechanisms of glioma genesis and identifying biomarkers for diagnosis and treatment.To help further investigations,we present a comprehensive database named GliomaDB.GliomaDB includes 21,086 samples from 4303 patients and integrates genomic,transcriptomic,epigenomic,clinical,and gene-drug association data regarding glioblastoma multiforme(GBM)and low-grade glioma(LGG)from The Cancer Genome Atlas(TCGA),Gene Expression Omnibus(GEO),the Chinese Glioma Genome Atlas(CGGA),the Memorial Sloan Kettering Cancer Center Integrated Mutation Profiling of Actionable Cancer Targets(MSK-IMPACT),the US Food and Drug Administration(FDA),and Pharm GKB.GliomaDB offers a user-friendly interface for two main types of functionalities.The first comprises queries of(i)somatic mutations,(ii)gene expression,(iii)microRNA(miRNA)expression,and(iv)DNA methylation.In addition,queries can be executed at the gene,region,and base level.Second,GliomaDB allows users to perform survival analysis,coexpression network visualization,multi-omics data visualization,and targeted drug recommendations based on personalized variations.GliomaDB bridges the gap between glioma genomics big data and the delivery of integrated information for end users,thus enabling both researchers and clinicians to effectively use publicly available data and empowering the progression of precision medicine in glioma.GliomaDB is freely accessible at http://bigd.big.ac.cn/glioma DB.

Biological Databases for Hematology Research

With the advances of genome-wide sequencing technologies and bioinformatics approaches, a large number of datasets of normal and malignant erythropoiesis have been gener- ated and made public to researchers around the world. Collection and integration of these datasets greatly facilitate basic research and clinical diagnosis and treatment of blood disorders. Here we provide a brief introduction of the most popular omics data resources of normal and malignant hematopoiesis, including some integrated web tools, to help users get better equipped to perform common analyses. We hope this review will promote the awareness and facilitate the usage of public