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George Church

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https://www.readbyqxmd.com/read/27918539/rapidly-evolving-homing-crispr-barcodes
#1
Reza Kalhor, Prashant Mali, George M Church
We present an approach for engineering evolving DNA barcodes in living cells. A homing guide RNA (hgRNA) scaffold directs the Cas9-hgRNA complex to the DNA locus of the hgRNA itself. We show that this homing CRISPR-Cas9 system acts as an expressed genetic barcode that diversifies its sequence and that the rate of diversification can be controlled in cultured cells. We further evaluate these barcodes in cell populations and show that they can be used to record lineage history and that the barcode RNA can be amplified in situ, a prerequisite for in situ sequencing...
December 5, 2016: Nature Methods
https://www.readbyqxmd.com/read/27909236/sexual-risk-behaviors-of-african-american-adolescent-females-the-role-of-cognitive-and-religious-factors
#2
Safiya George Dalmida, Natasha Aduloju-Ajijola, Dora Clayton-Jones, Tami L Thomas, Ricardo J Erazo Toscano, Rashunda Lewis, Terri Fleming, Shirley Taylor, Macie Lunyong
INTRODUCTION: African American (AA) high school-age girls are more likely to have had sex before age 13 years and have higher rates of all sexually transmitted infections. Cognition and religion/spirituality are associated with adolescent sexuality, therefore, the purpose of this study was to identify cognitive and religious substrates of AA girls' risky sexual behaviors. METHOD: A descriptive study was conducted with 65 AA girls aged 15 to 20 years using computerized questionnaires and cognitive function tasks...
November 30, 2016: Journal of Transcultural Nursing: Official Journal of the Transcultural Nursing Society
https://www.readbyqxmd.com/read/27888789/reliability-and-minimal-detectable-change-in-foot-pressure-measurements-in-typically-developing-children
#3
Timothy Niiler, Chris Church, Nancy Lennon, John Henley, Ameeka George, Daveda Taylor, Angelica Montes, Freeman Miller
BACKGROUND: In pedobarography, clinically meaningful comparison of measurements within or between subjects is limited by data variability and measurement error. This study aims to determine the components of the minimal detectable change (MDC) in impulse across all foot regions and the reliability of these measures. METHODS: A convenience sample of foot pressures from 108 visits by normal, healthy subjects aged 2-17 years was studied. Each subject had three pedobarograph measurements taken per foot, with six subjects returning for a second visit for assessment of day-to-day variability...
October 22, 2016: Foot
https://www.readbyqxmd.com/read/27882922/an-ethnically-relevant-consensus-korean-reference-genome-is-a-step-towards-personal-reference-genomes
#4
Yun Sung Cho, Hyunho Kim, Hak-Min Kim, Sungwoong Jho, JeHoon Jun, Yong Joo Lee, Kyun Shik Chae, Chang Geun Kim, Sangsoo Kim, Anders Eriksson, Jeremy S Edwards, Semin Lee, Byung Chul Kim, Andrea Manica, Tae-Kwang Oh, George M Church, Jong Bhak
Human genomes are routinely compared against a universal reference. However, this strategy could miss population-specific and personal genomic variations, which may be detected more efficiently using an ethnically relevant or personal reference. Here we report a hybrid assembly of a Korean reference genome (KOREF) for constructing personal and ethnic references by combining sequencing and mapping methods. We also build its consensus variome reference, providing information on millions of variants from 40 additional ethnically homogeneous genomes from the Korean Personal Genome Project...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27804970/engineering-and-optimising-deaminase-fusions-for-genome-editing
#5
Luhan Yang, Adrian W Briggs, Wei Leong Chew, Prashant Mali, Marc Guell, John Aach, Daniel Bryan Goodman, David Cox, Yinan Kan, Emal Lesha, Venkataramanan Soundararajan, Feng Zhang, George Church
Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2...
November 2, 2016: Nature Communications
https://www.readbyqxmd.com/read/27782796/complete-mitochondrial-genomes-of-living-and-extinct-pigeons-revise-the-timing-of-the-columbiform-radiation
#6
André E R Soares, Ben J Novak, James Haile, Tim H Heupink, Jon Fjeldså, M Thomas P Gilbert, Hendrik Poinar, George M Church, Beth Shapiro
BACKGROUND: Pigeons and doves (Columbiformes) are one of the oldest and most diverse extant lineages of birds. However, the nature and timing of the group's evolutionary radiation remains poorly resolved, despite recent advances in DNA sequencing and assembly and the growing database of pigeon mitochondrial genomes. One challenge has been to generate comparative data from the large number of extinct pigeon lineages, some of which are morphologically unique and therefore difficult to place in a phylogenetic context...
October 26, 2016: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/27730198/a-randomised-open-label-study-of-umeclidinium-versus-glycopyrronium-in-patients-with-copd
#7
Tara Rheault, Sanjeev Khindri, Mitra Vahdati-Bolouri, Alison Church, William A Fahy
This study compared the efficacy and safety of once-daily umeclidinium 62.5 µg with once-daily glycopyrronium 50 µg in patients with moderate-to-severe chronic obstructive pulmonary disease. This was a 12-week, multicentre, randomised, open-label, parallel-group study (Clinicaltrials.gov: NCT02236611). Patients were randomised 1:1 to umeclidinium 62.5 µg or glycopyrronium 50 µg administered via Ellipta or Breezhaler dry powder inhaler, respectively. The primary endpoint was trough forced expiratory volume in 1 s (FEV1) at day 85 in the per-protocol population...
April 2016: ERJ Open Research
https://www.readbyqxmd.com/read/27729524/design-and-characterization-of-a-nanopore-coupled-polymerase-for-single-molecule-dna-sequencing-by-synthesis-on-an-electrode-array
#8
P Benjamin Stranges, Mirkó Palla, Sergey Kalachikov, Jeff Nivala, Michael Dorwart, Andrew Trans, Shiv Kumar, Mintu Porel, Minchen Chien, Chuanjuan Tao, Irina Morozova, Zengmin Li, Shundi Shi, Aman Aberra, Cleoma Arnold, Alexander Yang, Anne Aguirre, Eric T Harada, Daniel Korenblum, James Pollard, Ashwini Bhat, Dmitriy Gremyachinskiy, Arek Bibillo, Roger Chen, Randy Davis, James J Russo, Carl W Fuller, Stefan Roever, Jingyue Ju, George M Church
Scalable, high-throughput DNA sequencing is a prerequisite for precision medicine and biomedical research. Recently, we presented a nanopore-based sequencing-by-synthesis (Nanopore-SBS) approach, which used a set of nucleotides with polymer tags that allow discrimination of the nucleotides in a biological nanopore. Here, we designed and covalently coupled a DNA polymerase to an α-hemolysin (αHL) heptamer using the SpyCatcher/SpyTag conjugation approach. These porin-polymerase conjugates were inserted into lipid bilayers on a complementary metal oxide semiconductor (CMOS)-based electrode array for high-throughput electrical recording of DNA synthesis...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27724973/the-whole-genome-sequences-and-experimentally-phased-haplotypes-of-over-100-personal-genomes
#9
Qing Mao, Serban Ciotlos, Rebecca Yu Zhang, Madeleine P Ball, Robert Chin, Paolo Carnevali, Nina Barua, Staci Nguyen, Misha R Agarwal, Tom Clegg, Abram Connelly, Ward Vandewege, Alexander Wait Zaranek, Preston W Estep, George M Church, Radoje Drmanac, Brock A Peters
BACKGROUND: Since the completion of the Human Genome Project in 2003, it is estimated that more than 200,000 individual whole human genomes have been sequenced. A stunning accomplishment in such a short period of time. However, most of these were sequenced without experimental haplotype data and are therefore missing an important aspect of genome biology. In addition, much of the genomic data is not available to the public and lacks phenotypic information. FINDINGS: As part of the Personal Genome Project, blood samples from 184 participants were collected and processed using Complete Genomics' Long Fragment Read technology...
October 11, 2016: GigaScience
https://www.readbyqxmd.com/read/27650503/fto-genotype-and-weight-loss-systematic-review-and-meta-analysis-of-9563-individual-participant-data-from-eight-randomised-controlled-trials
#10
Katherine M Livingstone, Carlos Celis-Morales, George D Papandonatos, Bahar Erar, Jose C Florez, Kathleen A Jablonski, Cristina Razquin, Amelia Marti, Yoriko Heianza, Tao Huang, Frank M Sacks, Mathilde Svendstrup, Xuemei Sui, Timothy S Church, Tiina Jääskeläinen, Jaana Lindström, Jaakko Tuomilehto, Matti Uusitupa, Tuomo Rankinen, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, Thorkild I A Sørensen, Lu Qi, George A Bray, Miguel A Martinez-Gonzalez, J Alfredo Martinez, Paul W Franks, Jeanne M McCaffery, Jose Lara, John C Mathers
OBJECTIVE:  To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials. DESIGN:  Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials. DATA SOURCES:  Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015. ELIGIBILITY CRITERIA FOR STUDY SELECTION:  Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions...
2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/27601680/emergent-rules-for-codon-choice-elucidated-by-editing-rare-arginine-codons-in-escherichia-coli
#11
Michael G Napolitano, Matthieu Landon, Christopher J Gregg, Marc J Lajoie, Lakshmi Govindarajan, Joshua A Mosberg, Gleb Kuznetsov, Daniel B Goodman, Oscar Vargas-Rodriguez, Farren J Isaacs, Dieter Söll, George M Church
The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 "recalcitrant" AGRs required diversification to identify viable alternatives...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27595405/a-multifunctional-aav-crispr-cas9-and-its-host-response
#12
Wei Leong Chew, Mohammadsharif Tabebordbar, Jason K W Cheng, Prashant Mali, Elizabeth Y Wu, Alex H M Ng, Kexian Zhu, Amy J Wagers, George M Church
CRISPR-Cas9 delivery by adeno-associated virus (AAV) holds promise for gene therapy but faces critical barriers on account of its potential immunogenicity and limited payload capacity. Here, we demonstrate genome engineering in postnatal mice using AAV-split-Cas9, a multifunctional platform customizable for genome editing, transcriptional regulation, and other previously impracticable applications of AAV-CRISPR-Cas9. We identify crucial parameters that impact efficacy and clinical translation of our platform, including viral biodistribution, editing efficiencies in various organs, antigenicity, immunological reactions, and physiological outcomes...
October 2016: Nature Methods
https://www.readbyqxmd.com/read/27551006/crispr-cas9-system-opportunities-and-concerns
#13
Stella K Vasiliou, Eleftherios P Diamandis, George M Church, Henry T Greely, Françoise Baylis, Charis Thompson, Gerold Schmitt-Ulms
No abstract text is available yet for this article.
October 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27540174/design-synthesis-and-testing-toward-a-57-codon-genome
#14
Nili Ostrov, Matthieu Landon, Marc Guell, Gleb Kuznetsov, Jun Teramoto, Natalie Cervantes, Minerva Zhou, Kerry Singh, Michael G Napolitano, Mark Moosburner, Ellen Shrock, Benjamin W Pruitt, Nicholas Conway, Daniel B Goodman, Cameron L Gardner, Gary Tyree, Alexandra Gonzales, Barry L Wanner, Julie E Norville, Marc J Lajoie, George M Church
Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect...
August 19, 2016: Science
https://www.readbyqxmd.com/read/27376770/nanoscale-imaging-of-rna-with-expansion-microscopy
#15
Fei Chen, Asmamaw T Wassie, Allison J Cote, Anubhav Sinha, Shahar Alon, Shoh Asano, Evan R Daugharthy, Jae-Byum Chang, Adam Marblestone, George M Church, Arjun Raj, Edward S Boyden
The ability to image RNA identity and location with nanoscale precision in intact tissues is of great interest for defining cell types and states in normal and pathological biological settings. Here, we present a strategy for expansion microscopy of RNA. We developed a small-molecule linker that enables RNA to be covalently attached to a swellable polyelectrolyte gel synthesized throughout a biological specimen. Then, postexpansion, fluorescent in situ hybridization (FISH) imaging of RNA can be performed with high yield and specificity as well as single-molecule precision in both cultured cells and intact brain tissue...
August 2016: Nature Methods
https://www.readbyqxmd.com/read/27284167/molecular-recordings-by-directed-crispr-spacer-acquisition
#16
Seth L Shipman, Jeff Nivala, Jeffrey D Macklis, George M Church
The ability to write a stable record of identified molecular events into a specific genomic locus would enable the examination of long cellular histories and have many applications, ranging from developmental biology to synthetic devices. We show that the type I-E CRISPR (clustered regularly interspaced short palindromic repeats)-Cas system of Escherichia coli can mediate acquisition of defined pieces of synthetic DNA. We harnessed this feature to generate records of specific DNA sequences into a population of bacterial genomes...
July 29, 2016: Science
https://www.readbyqxmd.com/read/27274218/a-randomized-parallel-group-study-to-evaluate-the-efficacy-of-umeclidinium-vilanterol-62-5-25-%C3%AE-g-on-health-related-quality-of-life-in-patients-with-copd
#17
Thomas M Siler, Alison C Donald, Dianne O'Dell, Alison Church, William A Fahy
BACKGROUND: The combination of the inhaled muscarinic antagonist umeclidinium (UMEC) with the long-acting β2-agonist vilanterol (VI) has been shown to provide significant improvements in lung function compared with UMEC, VI, or placebo (PBO) in patients with chronic obstructive pulmonary disease (COPD). This study was specifically designed to support these findings by assessing health-related quality of life and symptomatic outcomes in a similar population. METHODS: This was a 12-week multicenter, randomized, double-blind, parallel-group, placebo-controlled study...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27271295/extensive-sequencing-of-seven-human-genomes-to-characterize-benchmark-reference-materials
#18
COMMENT
Justin M Zook, David Catoe, Jennifer McDaniel, Lindsay Vang, Noah Spies, Arend Sidow, Ziming Weng, Yuling Liu, Christopher E Mason, Noah Alexander, Elizabeth Henaff, Alexa B R McIntyre, Dhruva Chandramohan, Feng Chen, Erich Jaeger, Ali Moshrefi, Khoa Pham, William Stedman, Tiffany Liang, Michael Saghbini, Zeljko Dzakula, Alex Hastie, Han Cao, Gintaras Deikus, Eric Schadt, Robert Sebra, Ali Bashir, Rebecca M Truty, Christopher C Chang, Natali Gulbahce, Keyan Zhao, Srinka Ghosh, Fiona Hyland, Yutao Fu, Mark Chaisson, Chunlin Xiao, Jonathan Trow, Stephen T Sherry, Alexander W Zaranek, Madeleine Ball, Jason Bobe, Preston Estep, George M Church, Patrick Marks, Sofia Kyriazopoulou-Panagiotopoulou, Grace X Y Zheng, Michael Schnall-Levin, Heather S Ordonez, Patrice A Mudivarti, Kristina Giorda, Ying Sheng, Karoline Bjarnesdatter Rypdal, Marc Salit
The Genome in a Bottle Consortium, hosted by the National Institute of Standards and Technology (NIST) is creating reference materials and data for human genome sequencing, as well as methods for genome comparison and benchmarking. Here, we describe a large, diverse set of sequencing data for seven human genomes; five are current or candidate NIST Reference Materials. The pilot genome, NA12878, has been released as NIST RM 8398. We also describe data from two Personal Genome Project trios, one of Ashkenazim Jewish ancestry and one of Chinese ancestry...
June 7, 2016: Scientific Data
https://www.readbyqxmd.com/read/27256881/genome-engineering-the-genome-project-write
#19
Jef D Boeke, George Church, Andrew Hessel, Nancy J Kelley, Adam Arkin, Yizhi Cai, Rob Carlson, Aravinda Chakravarti, Virginia W Cornish, Liam Holt, Farren J Isaacs, Todd Kuiken, Marc Lajoie, Tracy Lessor, Jeantine Lunshof, Matthew T Maurano, Leslie A Mitchell, Jasper Rine, Susan Rosser, Neville E Sanjana, Pamela A Silver, David Valle, Harris Wang, Jeffrey C Way, Luhan Yang
No abstract text is available yet for this article.
July 8, 2016: Science
https://www.readbyqxmd.com/read/27248712/next-stop-for-the-crispr-revolution-rna-guided-epigenetic-regulators
#20
REVIEW
Suhani Vora, Marcelle Tuttle, Jenny Cheng, George Church
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins offer a breakthrough platform for cheap, programmable, and effective sequence-specific DNA targeting. The CRISPR-Cas system is naturally equipped for targeted DNA cutting through its native nuclease activity. As such, groups researching a broad spectrum of biological organisms have quickly adopted the technology with groundbreaking applications to genomic sequence editing in over 20 different species. However, the biological code of life is not only encoded in genetics but also in epigenetics as well...
September 2016: FEBS Journal
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