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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:15/0  |  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.


  
Collisional cooling of ultracold molecules 期刊论文
NATURE, 2020, 580 (7802) : 197-+
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:11/0  |  提交时间:2020/07/03

Since the original work on Bose-Einstein condensation(1,2), the use of quantum degenerate gases of atoms has enabled the quantum emulation of important systems in condensed matter and nuclear physics, as well as the study of many-body states that have no analogue in other fields of physics(3). Ultracold molecules in the micro- and nanokelvin regimes are expected to bring powerful capabilities to quantum emulation(4) and quantum computing(5), owing to their rich internal degrees of freedom compared to atoms, and to facilitate precision measurement and the study of quantum chemistry(6). Quantum gases of ultracold atoms can be created using collision-based cooling schemes such as evaporative cooling, but thermalization and collisional cooling have not yet been realized for ultracold molecules. Other techniques, such as the use of supersonic jets and cryogenic buffer gases, have reached temperatures limited to above 10 millikelvin(7,8). Here we show cooling of NaLi molecules to micro- and nanokelvin temperatures through collisions with ultracold Na atoms, with both molecules and atoms prepared in their stretched hyperfine spin states. We find a lower bound on the ratio of elastic to inelastic molecule-atom collisions that is greater than 50-large enough to support sustained collisional cooling. By employing two stages of evaporation, we increase the phase-space density of the molecules by a factor of 20, achieving temperatures as low as 220 nanokelvin. The favourable collisional properties of the Na-NaLi system could enable the creation of deeply quantum degenerate dipolar molecules and raises the possibility of using stretched spin states in the cooling of other molecules.


NaLi molecules are cooled to micro- and nanokelvin temperatures through collisions with ultracold Na atoms by using molecules and atoms in stretched hyperfine spin states and applying two evaporation stages.


  
Decoding the development of the human hippocampus 期刊论文
NATURE, 2020, 577 (7791) : 531-+
作者:  Zhong, Suijuan;  Ding, Wenyu;  Sun, Le;  Lu, Yufeng;  Dong, Hao;  Fan, Xiaoying;  Liu, Zeyuan;  Chen, Ruiguo;  Zhang, Shu;  Ma, Qiang;  Tang, Fuchou;  Wu, Qian;  Wang, Xiaoqun
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

The hippocampus is an important part of the limbic system in the human brain that has essential roles in spatial navigation and the consolidation of information from short-term memory to long-term memory(1,2). Here we use single-cell RNA sequencing and assay for transposase-accessible chromatin using sequencing (ATAC-seq) analysis to illustrate the cell types, cell linage, molecular features and transcriptional regulation of the developing human hippocampus. Using the transcriptomes of 30,416 cells from the human hippocampus at gestational weeks 16-27, we identify 47 cell subtypes and their developmental trajectories. We also identify the migrating paths and cell lineages of PAX6(+) and HOPX+ hippocampal progenitors, and regional markers of CA1, CA3 and dentate gyrus neurons. Multiomic data have uncovered transcriptional regulatory networks of the dentate gyrus marker PROX1. We also illustrate spatially specific gene expression in the developing human prefrontal cortex and hippocampus. The molecular features of the human hippocampus at gestational weeks 16-20 are similar to those of the mouse at postnatal days 0-5 and reveal gene expression differences between the two species. Transient expression of the primate-specific gene NBPF1 leads to a marked increase in PROX1(+) cells in the mouse hippocampus. These data provides a blueprint for understanding human hippocampal development and a tool for investigating related diseases.


Single-cell RNA sequencing is used to catalogue and explore the developmental trajectories of more than 30,000 cells in the developing human hippocampus.


  
The promise and challenge of therapeutic genome editing 期刊论文
NATURE, 2020, 578 (7794) : 229-236
作者:  Zhong, Suijuan;  Ding, Wenyu;  Sun, Le;  Lu, Yufeng;  Dong, Hao;  Fan, Xiaoying;  Liu, Zeyuan;  Chen, Ruiguo;  Zhang, Shu;  Ma, Qiang;  Tang, Fuchou;  Wu, Qian;  Wang, Xiaoqun
收藏  |  浏览/下载:37/0  |  提交时间:2020/07/03

Genome editing, which involves the precise manipulation of cellular DNA sequences to alter cell fates and organism traits, has the potential to both improve our understanding of human genetics and cure genetic disease. Here I discuss the scientific, technical and ethical aspects of using CRISPR (clustered regularly interspaced short palindromic repeats) technology for therapeutic applications in humans, focusing on specific examples that highlight both opportunities and challenges. Genome editing is-or will soon be-in the clinic for several diseases, with more applications under development. The rapid pace of the field demands active efforts to ensure that this breakthrough technology is used responsibly to treat, cure and prevent genetic disease.


  
Ground-to-satellite quantum teleportation 期刊论文
NATURE, 2017, 549 (7670) : 70-+
作者:  Ren, Ji-Gang;  Xu, Ping;  Yong, Hai-Lin;  Zhang, Liang;  Liao, Sheng-Kai;  Yin, Juan;  Liu, Wei-Yue;  Cai, Wen-Qi;  Yang, Meng;  Li, Li;  Yang, Kui-Xing;  Han, Xuan;  Yao, Yong-Qiang;  Li, Ji;  Wu, Hai-Yan;  Wan, Song;  Liu, Lei;  Liu, Ding-Quan;  Kuang, Yao-Wu;  He, Zhi-Ping;  Shang, Peng;  Guo, Cheng;  Zheng, Ru-Hua;  Tian, Kai;  Zhu, Zhen-Cai;  Liu, Nai-Le;  Lu, Chao-Yang;  Shu, Rong;  Chen, Yu-Ao;  Peng, Cheng-Zhi;  Wang, Jian-Yu;  Pan, Jian-Wei
收藏  |  浏览/下载:13/0  |  提交时间:2019/11/27
Layer-dependent ferromagnetism in a van der Waals crystal down to the monolayer limit 期刊论文
NATURE, 2017, 546 (7657) : 270-+
作者:  Huang, Bevin;  Clark, Genevieve;  Navarro-Moratalla, Efren;  Klein, Dahlia R.;  Cheng, Ran;  Seyler, Kyle L.;  Zhong, Ding;  Schmidgall, Emma;  McGuire, Michael A.;  Cobden, David H.;  Yao, Wang;  Xiao, Di;  Jarillo-Herrero, Pablo;  Xu, Xiaodong
收藏  |  浏览/下载:9/0  |  提交时间:2019/04/09
Integrated genomic and molecular characterization of cervical cancer 期刊论文
NATURE, 2017, 543 (7645) : 378-+
作者:  Burk, Robert D.;  Chen, Zigui;  Saller, Charles;  Tarvin, Katherine;  Carvalho, Andre L.;  Scapulatempo-Neto, Cristovam;  Silveira, Henrique C.;  Fregnani, Jose H.;  Creighton, Chad J.;  Anderson, Matthew L.;  Castro, Patricia;  Wang, Sophia S.;  Yau, Christina;  Benz, Christopher;  Robertson, A. Gordon;  Mungall, Karen;  Lim, Lynette;  Bowlby, Reanne;  Sadeghi, Sara;  Brooks, Denise;  Sipahimalani, Payal;  Mar, Richard;  Ally, Adrian;  Clarke, Amanda;  Mungall, Andrew J.;  Tam, Angela;  Lee, Darlene;  Chuah, Eric;  Schein, Jacqueline E.;  Tse, Kane;  Kasaian, Katayoon;  Ma, Yussanne;  Marra, Marco A.;  Mayo, Michael;  Balasundaram, Miruna;  Thiessen, Nina;  Dhalla, Noreen;  Carlsen, Rebecca;  Moore, Richard A.;  Holt, Robert A.;  Jones, Steven J. M.;  Wong, Tina;  Pantazi, Angeliki;  Parfenov, Michael;  Kucherlapati, Raju;  Hadjipanayis, Angela;  Seidman, Jonathan;  Kucherlapati, Melanie;  Ren, Xiaojia;  Xu, Andrew W.;  Yang, Lixing;  Park, Peter J.;  Lee, Semin;  Rabeno, Brenda;  Huelsenbeck-Dill, Lori;  Borowsky, Mark;  Cadungog, Mark;  Iacocca, Mary;  Petrelli, Nicholas;  Swanson, Patricia;  Ojesina, Akinyemi I.;  Le, Xuan;  Sandusky, George;  Adebamowo, Sally N.;  Akeredolu, Teniola;  Adebamowo, Clement;  Reynolds, Sheila M.;  Shmulevich, Ilya;  Shelton, Candace;  Crain, Daniel;  Mallery, David;  Curley, Erin;  Gardner, Johanna;  Penny, Robert;  Morris, Scott;  Shelton, Troy;  Liu, Jia;  Lolla, Laxmi;  Chudamani, Sudha;  Wu, Ye;  Birrer, Michael;  McLellan, Michael D.;  Bailey, Matthew H.;  Miller, Christopher A.;  Wyczalkowski, Matthew A.;  Fulton, Robert S.;  Fronick, Catrina C.;  Lu, Charles;  Mardis, Elaine R.;  Appelbaum, Elizabeth L.;  Schmidt, Heather K.;  Fulton, Lucinda A.;  Cordes, Matthew G.;  Li, Tiandao;  Ding, Li;  Wilson, Richard K.;  Rader, Janet S.;  Behmaram, Behnaz;  Uyar, Denise;  Bradley, William;  Wrangle, John;  Pastore, Alessandro;  Levine, Douglas A.;  Dao, Fanny;  Gao, Jianjiong;  Schultz, Nikolaus;  Sander, Chris;  Ladanyi, Marc;  Einstein, Mark;  Teeter, Randall;  Benz, Stephen;  Wentzensen, Nicolas;  Felau, Ina;  Zenklusen, Jean C.;  Bodelon, Clara;  Demchok, John A.;  Yang, Liming;  Sheth, Margi;  Ferguson, Martin L.;  Tarnuzzer, Roy;  Yang, Hannah;  Schiffman, Mark;  Zhang, Jiashan;  Wang, Zhining;  Davidsen, Tanja;  Olaniyan, Olayinka;  Hutter, Carolyn M.;  Sofia, Heidi J.;  Gordenin, Dmitry A.;  Chan, Kin;  Roberts, Steven A.;  Klimczak, Leszek J.;  Van Waes, Carter;  Chen, Zhong;  Saleh, Anthony D.;  Cheng, Hui;  Parfitt, Jeremy;  Bartlett, John;  Albert, Monique;  Arnaout, Angel;  Sekhon, Harman;  Gilbert, Sebastien;  Peto, Myron;  Myers, Jerome;  Harr, Jodi;  Eckman, John;  Bergsten, Julie;  Tucker, Kelinda;  Zach, Leigh Anne;  Karlan, Beth Y.;  Lester, Jenny;  Orsulic, Sandra;  Sun, Qiang;  Naresh, Rashi;  Pihl, Todd;  Wan, Yunhu;  Zaren, Howard;  Sapp, Jennifer;  Miller, Judy;  Drwiega, Paul;  Ojesina, Akinyemi I.;  Murray, Bradley A.;  Zhang, Hailei;  Cherniack, Andrew D.;  Sougnez, Carrie;  Pedamallu, Chandra Sekhar;  Lichtenstein, Lee;  Meyerson, Matthew;  Noble, Michael S.;  Heiman, David I.;  Voet, Doug;  Getz, Gad;  Saksena, Gordon;  Kim, Jaegil;  Shih, Juliann;  Cho, Juok;  Lawrence, Michael S.;  Gehlenborg, Nils;  Lin, Pei;  Beroukhim, Rameen;  Frazer, Scott;  Gabriel, Stacey B.;  Schumacher, Steven E.;  Leraas, Kristen M.;  Lichtenberg, Tara M.;  Zmuda, Erik;  Bowen, Jay;  Frick, Jessica;  Gastier-Foster, Julie M.;  Wise, Lisa;  Gerken, Mark;  Ramirez, Nilsa C.;  Danilova, Ludmila;  Cope, Leslie;  Baylin, Stephen B.;  Salvesen, Helga B.;  Vellano, Christopher P.;  Ju, Zhenlin;  Diao, Lixia;  Zhao, Hao;  Chong, Zechen;  Ryan, Michael C.;  Martinez-Ledesma, Emmanuel;  Verhaak, Roeland G.;  Byers, Lauren Averett;  Yuan, Yuan;  Chen, Ken;  Ling, Shiyun;  Mills, Gordon B.;  Lu, Yiling;  Akbani, Rehan;  Seth, Sahil;  Liang, Han;  Wang, Jing;  Han, Leng;  Weinstein, John N.;  Bristow, Christopher A.;  Zhang, Wei;  Mahadeshwar, Harshad S.;  Sun, Huandong;  Tang, Jiabin;  Zhang, Jianhua;  Song, Xingzhi;  Protopopov, Alexei;  Shaw, Kenna R. Mills;  Chin, Lynda;  Olabode, Oluwole;  Ojesina, Akinyemi I.;  DiSaia, Philip;  Radenbaugh, Amie;  Haussler, David;  Zhu, Jingchun;  Stuart, Josh;  Chalise, Prabhakar;  Koestler, Devin;  Fridley, Brooke L.;  Godwin, Andrew K.;  Madan, Rashna;  Ciriello, Giovanni;  Martinez, Cathleen;  Higgins, Kelly;  Bocklage, Therese;  Auman, J. Todd;  Perou, Charles M.;  Tan, Donghui;  Parker, Joel S.;  Hoadley, Katherine A.;  Wilkerson, Matthew D.;  Mieczkowski, Piotr A.;  Skelly, Tara;  Veluvolu, Umadevi;  Hayes, D. Neil;  Rathmell, W. Kimryn;  Hoyle, Alan P.;  Simons, Janae V.;  Wu, Junyuan;  Mose, Lisle E.;  Soloway, Matthew G.;  Balu, Saianand;  Meng, Shaowu;  Jefferys, Stuart R.;  Bodenheimer, Tom;  Shi, Yan;  Roach, Jeffrey;  Thorne, Leigh B.;  Boice, Lori;  Huang, Mei;  Jones, Corbin D.;  Zuna, Rosemary;  Walker, Joan;  Gunderson, Camille;  Snowbarger, Carie;  Brown, David;  Moxley, Katherine;  Moore, Kathleen;  Andrade, Kelsi;  Landrum, Lisa;  Mannel, Robert;  McMeekin, Scott;  Johnson, Starla;  Nelson, Tina;  Elishaev, Esther;  Dhir, Rajiv;  Edwards, Robert;  Bhargava, Rohit;  Tiezzi, Daniel G.;  Andrade, Jurandyr M.;  Noushmehr, Houtan;  Carlotti, Carlos Gilberto, Jr.;  Tirapelli, Daniela Pretti da Cunha;  Weisenberger, Daniel J.;  Van Den Berg, David J.;  Maglinte, Dennis T.;  Bootwalla, Moiz S.;  Lai, Phillip H.;  Triche, Timothy, Jr.;  Swisher, Elizabeth M.;  Agnew, Kathy J.;  Shelley, Carl Simon;  Laird, Peter W.;  Schwarz, Julie;  Grigsby, Perry;  Mutch, David
收藏  |  浏览/下载:14/0  |  提交时间:2019/04/09