The Reproducibility of Lists of Differentially Expressed Genes in Microarray Studies

Reproducibility is a fundamental requirement in scientific experiments and clinical contexts. Recent publications raise concerns about the reliability of microarray technology because of the apparent lack of agreement between lists of differentially expressed genes (DEGs). In this study we demonstrate that (1) such discordance may stem from ranking and selecting DEGs solely by statistical significance (P) derived from widely used simple t-tests; (2) when fold change (FC) is used as the ranking criterion, the lists become much more reproducible, especially when fewer genes are selected; and (3) the instability of short DEG lists based on P cutoffs is an expected mathematical consequence of the high variability of the t-values. We recommend the use of FC ranking plus a non-stringent P cutoff as a baseline practice in order to generate more reproducible DEG lists. The FC criterion enhances reproducibility while the P criterion balances sensitivity and specificity

Critical Epitopes in the Nucleocapsid Protein of SFTS Virus Recognized by a Panel of SFTS Patients Derived Human Monoclonal Antibodies

BACKGROUND: SFTS virus (SFTSV) is a newly discovered pathogen to cause severe fever with thrombocytopenia syndrome (SFTS) in human. Successful control of SFTSV epidemic requires better understanding of the antigen target in humoral immune responses to the new bunyavirus infection. METHODOLOGY/PRINCIPAL FINDINGS: We have generated a combinatorial Fab antibody phage library from two SFTS patients recovered from SFTSV infection. To date, 94 unique human antibodies have been generated and characterized from over 1200 Fab antibody clones obtained by screening the library with SFTS purified virions. All those monoclonal antibodies (MAbs) recognized the nucleocapsid (N) protein of SFTSV while none of them were reactive to the viral glycoproteins Gn or Gc. Furthermore, over screening 1000 mouse monoclonal antibody clones derived from SFTSV virions immunization, 462 clones reacted with N protein, while only 16 clones were reactive to glycoprotein. Furthermore, epitope mapping of SFTSV N protein was performed through molecular simulation, site mutation and competitive ELISA, and we found that at least 4 distinct antigenic epitopes within N protein were recognized by those human and mouse MAbs, in particular mutation of Glu10 to Ala10 abolished or significantly reduced the binding activity of nearly most SFTS patients derived MAbs. CONCLUSIONS/SIGNIFICANCE: The large number of human recombinant MAbs derived from SFTS patients recognized the viral N protein indicated the important role of the N protein in humoral responses to SFTSV infection, and the critical epitopes we defined in this study provided molecular basis for detection and diagnosis of SFTSV infection

The balance of reproducibility, sensitivity, and specificity of lists of differentially expressed genes in microarray studies

<p>Abstract</p> <p>Background</p> <p>Reproducibility is a fundamental requirement in scientific experiments. Some recent publications have claimed that microarrays are unreliable because lists of differentially expressed genes (DEGs) are not reproducible in similar experiments. Meanwhile, new statistical methods for identifying DEGs continue to appear in the scientific literature. The resultant variety of existing and emerging methods exacerbates confusion and continuing debate in the microarray community on the appropriate choice of methods for identifying reliable DEG lists.</p> <p>Results</p> <p>Using the data sets generated by the MicroArray Quality Control (MAQC) project, we investigated the impact on the reproducibility of DEG lists of a few widely used gene selection procedures. We present comprehensive results from inter-site comparisons using the same microarray platform, cross-platform comparisons using multiple microarray platforms, and comparisons between microarray results and those from TaqMan – the widely regarded "standard" gene expression platform. Our results demonstrate that (1) previously reported discordance between DEG lists could simply result from ranking and selecting DEGs solely by statistical significance (<it>P</it>) derived from widely used simple <it>t</it>-tests; (2) when fold change (FC) is used as the ranking criterion with a non-stringent <it>P</it>-value cutoff filtering, the DEG lists become much more reproducible, especially when fewer genes are selected as differentially expressed, as is the case in most microarray studies; and (3) the instability of short DEG lists solely based on <it>P</it>-value ranking is an expected mathematical consequence of the high variability of the <it>t</it>-values; the more stringent the <it>P</it>-value threshold, the less reproducible the DEG list is. These observations are also consistent with results from extensive simulation calculations.</p> <p>Conclusion</p> <p>We recommend the use of FC-ranking plus a non-stringent <it>P </it>cutoff as a straightforward and baseline practice in order to generate more reproducible DEG lists. Specifically, the <it>P</it>-value cutoff should not be stringent (too small) and FC should be as large as possible. Our results provide practical guidance to choose the appropriate FC and <it>P</it>-value cutoffs when selecting a given number of DEGs. The FC criterion enhances reproducibility, whereas the <it>P </it>criterion balances sensitivity and specificity.</p

Research on optimisation of minimum air clearance of 1000 kV UHV AC substation

Based on air clearance discharge characteristic curve and insulation coordination method, it is pointed out that the minimum air clearance of 1000 kV ultra-high voltage (UHV) AC substation can be further optimised. On the basis of analysis of the merits and demerits of the two insulation coordination methods for air clearances of UHV substation stated in the national standard GB/Z 24842–2009, it is concluded that using statistical method for insulation coordination is more reasonable and feasible. The minimum air clearance of UHV substation is optimised with the statistical method based on 1000 μs switching impulse characteristic test results. According to the study results, the phase-to-earth air clearance A1′ can be 1 m less than that specified in standard, the air clearance between conductors 0.5 m less than that specified in standard, and the phase-to-phase air clearance of grading ring and tubular bus 0.6 and 1.8 m, respectively, less than that specified in standard

Research on overvoltage and minimum air clearance on 1000 kV AC side of converter transformer in ±1100 kV Guquan converter station

In the hierarchically connected ultra-high voltage (UHV) DC projects, the minimum air clearance on the 1000 kV AC side of converter transformer directly affects the layout and area of the valve hall. The minimum air clearance is determined by the overvoltage and the flashover characteristics of different electrodes. Since the UHV DC projects are hierarchically connected to the AC power grid, the overvoltage and the electrode flashover characteristics are different from that of general UHV AC projects, necessitating the relevant overvoltage calculation and test studies. The electromagnetic transients software PSCAD is used for modelling of the ±1100 kV Wannan convertor station and the related AC system. The power frequency overvoltage, switching overvoltage, time-to-crest value, and coefficient α of phase-to-phase overvoltage on the AC side of the 1000 kV converter transformer are calculated. Tests are carried out on air clearances between bundle conductors, tubular buses, and equipment grading rings under switching impulse with 1000 μs long wave-front. The minimum phase-to-earth and phase-to-phase air clearances on the 1000 kV AC side of the converter transformer are given

Study of the best decocting time of sun dried ginseng by using the hyperspectral imaging technology

In this research, a new method based on the hyperspectral imaging for searching the best decocting time of sun dried ginseng is reported. The spectral images at different decocting time of test sample have been taken by the staring hyperspectral fluorescence imaging system and the solubility of active ingredients have been discussed by analyzing the changes on the spectral curves. The spectral range of the system is 400–720nm and the spectral resolution is 5nm. In the decocting process, the active ingredients of nonsoaked ginseng was dissolved in the tissue fluid at first, and reached equilibrium condition at last after the precipitation–dissolution reciprocating process of boiling. At last, the experimental results show that the best decoction time of sun dried ginseng is about 60min after boiling

Semi-quantitative analysis on the content of berberine hydrochloride in compound berberine tablets with the fluorescence spectral imaging method

The content of berberine hydrochloride (BH) in compound berberine tablets (CBTs) is subject to strict requirements. Its content is usually measured based on chemical analysis. In this paper, the fluorescence spectral imaging method was used to study the relative content of BH from a physics perspective. By comparing the relative fluorescence intensity of self-made CBTs with different mass percentages of BH, a linear positive relationship was observed between the BH content and the relative fluorescence intensity, and accordingly the quality of CBTs of different brands was evaluated. The results indicate that the fluorescence spectral imaging method can be a simple, fast and nondestructive semi-quantitative analysis method to determine the content of BH in CBTs, and this method has great potential in the quality control of CBTs

Hypertension Subtypes, Mortality Risk, and Differential Effects Between Two Hypertension Guidelines

AIM: To examine which hypertension subtypes are primarily responsible for the difference in the hypertension prevalence and treatment recommendations, and to assess their mortality risk if 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guideline were adopted among Chinese adults. METHODS: We used the nationally representative data of China Health and Retirement Longitudinal Study (CHARLS) to estimate the differences in the prevalence of isolated systolic hypertension (ISH), systolic diastolic hypertension (SDH) and isolated diastolic hypertension (IDH) between the 2017 ACC/AHA and the 2018 China Hypertension League (CHL) guidelines. We further assessed their mortality risk using follow-up data from the China Health and Nutrition Survey (CHNS) by the Cox model. RESULTS: The increase from the 2017 ACC/AHA guideline on hypertension prevalence was mostly from SDH (8.64% by CHL to 25.59% by ACC/AHA), followed by IDH (2.42 to 6.93%). However, the difference was minuscule in the proportion of people recommended for antihypertensive treatment among people with IDH (2.42 to 3.34%) or ISH (12.00 to 12.73%). Among 22,184 participants with a median follow-up of 6.14 years from CHNS, attenuated but significant associations were observed between all-cause mortality and SDH (hazard ratio 1.56; 95% CI: 1.36,1.79) and ISH (1.29; 1.03,1.61) by ACC/AHA but null association for IDH (1.15; 0.98,1.35). CONCLUSION: Adoption of the 2017 ACC/AHA may be applicable to improve the unacceptable hypertension control rate among Chinese adults but with cautions for the drug therapy among millions of subjects with IDH

Remaining Oil Distribution Law and Development Potential Analysis after Polymer Flooding Based on Reservoir Architecture in Daqing Oilfield, China

Polymer flooding has drawn more and more attention in the world for its high incremental oil recovery factor and relative low costs compared with water flooding and other chemically enhanced oil recovery techniques. However, for many oilfields, such as Daqing Oilfield, China, that have already been flooded with polymers, how to further improve recovery remains a big problem. Traditional intralayer, interlayer and plane heterogeneity studies cannot accurately characterize the remaining oil distribution after polymer flooding. To solve this problem, we established a method to quantitatively describe the reservoir’s architecture. Then, the architecture elements were dissected hierarchically and the interface of each architecture level in Daqing Oilfield was identified. The distribution pattern and development potential of the remaining oil after polymer flooding under the influence of reservoir architecture was analyzed. The results show that, regarding the sedimentary process from north to south in Daqing Oilfield, the channel becomes narrower, the thickness decreases, the point bar’s width increases and the thickness of the meandering river decreases. The braided bar scale becomes larger and the thickness becomes smaller in the braided river. According to the reservoir’s architecture, the remaining oil was divided into four categories of plane remaining oil (abandoned channel occlusion type, interfluvial sand body occlusion type, inter-well retention type and well pattern uncontrollable type) and three types of vertical remaining oil (in-layer interlayer occlusion type, rhythm type and gravity type). About 40% of the original oil in place (OOIP) of Daqing Oilfield has not yet been produced, which indicates that there is great potential for development. This study is important for improving oil recovery in polymer-flooded reservoirs