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Integrating genomic features for non-invasive early lung cancer detection 期刊论文
NATURE, 2020, 580 (7802) : 245-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:17/0  |  提交时间:2020/07/03

Circulating tumour DNA in blood is analysed to identify genomic features that distinguish early-stage lung cancer patients from risk-matched controls, and these are integrated into a machine-learning method for blood-based lung cancer screening.


Radiologic screening of high-risk adults reduces lung-cancer-related mortality(1,2)  however, a small minority of eligible individuals undergo such screening in the United States(3,4). The availability of blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)(5), a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed '  lung cancer likelihood in plasma'  (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.


  
Hidden cost of conservation: A demonstration using losses from human-wildlife conflicts under a payments for ecosystem services program 期刊论文
ECOLOGICAL ECONOMICS, 2020, 169
作者:  Yang, Hongbo;  Lupi, Frank;  Zhang, Jindong;  Liu, Jianguo
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/02
Conservation costs  Grain-to-Green Program  Human-wildlife conflict  Impact evaluation  Matching  
A claustrum in reptiles and its role in slow-wave sleep 期刊论文
NATURE, 2020, 578 (7795) : 413-+
作者:  Loubeyre, Paul;  Occelli, Florent;  Dumas, Paul
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

The mammalian claustrum, owing to its widespread connectivity with other forebrain structures, has been hypothesized to mediate functions that range from decision-making to consciousness(1). Here we report that a homologue of the claustrum, identified by single-cell transcriptomics and viral tracing of connectivity, also exists in a reptile-the Australian bearded dragon Pogona vitticeps. In Pogona, the claustrum underlies the generation of sharp waves during slow-wave sleep. The sharp waves, together with superimposed high-frequency ripples(2), propagate to the entire neighbouring pallial dorsal ventricular ridge (DVR). Unilateral or bilateral lesions of the claustrum suppress the production of sharp-wave ripples during slow-wave sleep in a unilateral or bilateral manner, respectively, but do not affect the regular and rapidly alternating sleep rhythm that is characteristic of sleep in this species(3). The claustrum is thus not involved in the generation of the sleep rhythm itself. Tract tracing revealed that the reptilian claustrum projects widely to a variety of forebrain areas, including the cortex, and that it receives converging inputs from, among others, areas of the mid- and hindbrain that are known to be involved in wake-sleep control in mammals(4-6). Periodically modulating the concentration of serotonin in the claustrum, for example, caused a matching modulation of sharp-wave production there and in the neighbouring DVR. Using transcriptomic approaches, we also identified a claustrum in the turtle Trachemys scripta, a distant reptilian relative of lizards. The claustrum is therefore an ancient structure that was probably already present in the brain of the common vertebrate ancestor of reptiles and mammals. It may have an important role in the control of brain states owing to the ascending input it receives from the mid- and hindbrain, its widespread projections to the forebrain and its role in sharp-wave generation during slow-wave sleep.


A structure homologous to the mammalian claustrum exists in reptiles and has a role in generating sharp waves in the brain during slow-wave sleep.


  
Targeting of temperate phages drives loss of type I CRISPR-Cas systems 期刊论文
NATURE, 2020, 578 (7793) : 149-+
作者:  Xiang, Lifeng;  Yin, Yu;  Zheng, Yun;  Ma, Yanping;  Li, Yonggang;  Zhao, Zhigang;  Guo, Junqiang;  Ai, Zongyong;  Niu, Yuyu;  Duan, Kui;  He, Jingjing;  Ren, Shuchao;  Wu, Dan;  Bai, Yun;  Shang, Zhouchun;  Dai, Xi;  Ji, Weizhi;  Li, Tianqing
收藏  |  浏览/下载:40/0  |  提交时间:2020/07/03

On infection of their host, temperate viruses that infect bacteria (bacteriophages  hereafter referred to as phages) enter either a lytic or a lysogenic cycle. The former results in lysis of bacterial cells and phage release (resulting in horizontal transmission), whereas lysogeny is characterized by the integration of the phage into the host genome, and dormancy (resulting in vertical transmission)(1). Previous co-culture experiments using bacteria and mutants of temperate phages that are locked in the lytic cycle have shown that CRISPR-Cas systems can efficiently eliminate the invading phages(2,3). Here we show that, when challenged with wild-type temperate phages (which can become lysogenic), type I CRISPR-Cas immune systems cannot eliminate the phages from the bacterial population. Furthermore, our data suggest that, in this context, CRISPR-Cas immune systems are maladaptive to the host, owing to the severe immunopathological effects that are brought about by imperfect matching of spacers to the integrated phage sequences (prophages). These fitness costs drive the loss of CRISPR-Cas from bacterial populations, unless the phage carries anti-CRISPR (acr) genes that suppress the immune system of the host. Using bioinformatics, we show that this imperfect targeting is likely to occur frequently in nature. These findings help to explain the patchy distribution of CRISPR-Cas immune systems within and between bacterial species, and highlight the strong selective benefits of phage-encoded acr genes for both the phage and the host under these circumstances.


CRISPR-Cas systems cannot eliminate temperate bacteriophages from bacterial populations and-in this context-the systems impose immunopathological costs on the host, creating selective pressures that may explain their patchy distribution in bacteria.


  
Determining Characteristic Relative Permeability From Coreflooding Experiments: A Simplified Model Approach 期刊论文
WATER RESOURCES RESEARCH, 2019
作者:  Rabinovich, A.;  Anto-Darkwah, E.;  Mishra, A. M.
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
characteristic relative permeability  effective relative permeability  capillary heterogeneity  coreflooding simulation  CO2 coreflooding  history matching  
Smartphone and tablet effects in contingent valuation web surveys - No reason to worry? 期刊论文
ECOLOGICAL ECONOMICS, 2019, 165
作者:  Skeie, Magnus Aa;  Lindhjem, Henrik;  Skjeflo, Sofie;  Navrud, Stale
收藏  |  浏览/下载:10/0  |  提交时间:2019/11/27
Contingent valuation  Ecosystem services  Mobile device  Propensity score matching  Survey quality  
Value of playgrounds relative to green spaces: Matching evidence from property prices in Australia 期刊论文
LANDSCAPE AND URBAN PLANNING, 2019, 190
作者:  Breunig, Robert;  Hasan, Syed;  Whiteoak, Kym
收藏  |  浏览/下载:7/0  |  提交时间:2019/11/27
Property price  Playgrounds  Hedonic analysis  Matching  Australia  
Do residential building energy efficiency standards reduce energy consumption in China? - A data-driven method to validate the actual performance of building energy efficiency standards 期刊论文
ENERGY POLICY, 2019, 131: 82-98
作者:  Wang, Xia;  Feng, Wei;  Cai, Weiguang;  Ren, Hong;  Ding, Chao;  Zhou, Nan
收藏  |  浏览/下载:9/0  |  提交时间:2019/11/27
Effectiveness of residential building energy efficiency standards  Household electricity consumption  Propensity scores matching method  Micro household survey  
Can a carbon trading system promote the transformation of a low-carbon economy under the framework of the porter hypothesis? -Empirical analysis based on the PSM-DID method 期刊论文
ENERGY POLICY, 2019, 129: 930-938
作者:  Wang, Han;  Chen, Zhoupeng;  Wu, Xingyi;  Niea, Xin
收藏  |  浏览/下载:5/0  |  提交时间:2019/11/26
Carbon trading  Low-carbon economic transformation  Porter hypothesis  Propensity score Matching Difference in differences  
Are Prosumer Households That Much Different? Evidence From Stated Residential Energy Consumption in Germany 期刊论文
ECOLOGICAL ECONOMICS, 2019, 158: 101-115
作者:  Oberst, Christian A.;  Schmitz, Hendrik;  Madlener, Reinhard
收藏  |  浏览/下载:8/0  |  提交时间:2019/04/09
Prosumer households  Rebound  Propensity score matching  Residential energy consumption  Energy efficiency  Renewable energies