Nanotechnology Now







Heifer International

Wikipedia Affiliate Button


DHgate

Home > Press > Single-cell genome sequencing gets better: Most complete genome sequences from single E. coli cells and individual neurons from the human brain generated by new sequencing approach from UC San Diego bioengineers and colleagues

Bioengineers from the University of California, San Diego are leading the research team that has published a breakthrough single-cell genome sequencing technique that stands to improve our understanding of genomic diversity among cells from the same human brain. With the new approach, the researchers generated the most complete genome sequences published thus far from single E. coli cells and individual neurons from the human brain. The approach, called Microwell Displacement Amplification System, confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters. This work is published in the journal Nature Biotechnology on November 10, 2013. An animated video illustrating the technique is available upon request.

Credit: UC San Diego Jacobs School of Engineering
Bioengineers from the University of California, San Diego are leading the research team that has published a breakthrough single-cell genome sequencing technique that stands to improve our understanding of genomic diversity among cells from the same human brain. With the new approach, the researchers generated the most complete genome sequences published thus far from single E. coli cells and individual neurons from the human brain. The approach, called Microwell Displacement Amplification System, confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters. This work is published in the journal Nature Biotechnology on November 10, 2013. An animated video illustrating the technique is available upon request.

Credit: UC San Diego Jacobs School of Engineering

Abstract:
Researchers led by bioengineers at the University of California, San Diego have generated the most complete genome sequences from single E. coli cells and individual neurons from the human brain. The breakthrough comes from a new single-cell genome sequencing technique that confines genome amplification to fluid-filled wells with a volume of just 12 nanoliters.

Single-cell genome sequencing gets better: Most complete genome sequences from single E. coli cells and individual neurons from the human brain generated by new sequencing approach from UC San Diego bioengineers and colleagues

San Diego, CA | Posted on November 11th, 2013

The study is published in the journal Nature Biotechnology on November 10, 2013.

"Our preliminary data suggest that individual neurons from the same brain have different genetic compositions. This is a relatively new idea, and our approach will enable researchers to look at genomic differences between single cells with much finer detail," said Kun Zhang, a professor in the Department of Bioengineering at the UC San Diego Jacobs School of Engineering and the corresponding author on the paper.

The researchers report that the genome sequences of single cells generated using the new approach exhibited comparatively little "amplification bias," which has been the most significant technological obstacle facing single-cell genome sequencing in the past decade. This bias refers to the fact that the amplification step is uneven, with different regions of a genome being copied different numbers of times. This imbalance complicates many downstream genomic analyses, including assembly of genomes from scratch and identifying DNA content variations among cells from the same individual.

Single-cell Genome Sequencing

Sequencing the genomes of single cells is of great interest to researchers working in many different fields. For example, probing the genetic make-up of individual cells would help researchers identify and understand a wide range of organisms that cannot be easily grown in the lab from the bacteria that live within our digestive tracts and on our skin, to the microscopic organisms that live in ocean water. Single-cell genetic studies are also being used to study cancer cells, stem cells and the human brain, which is made up of cells that increasingly appear to have significant genomic diversity.

"We now have the wonderful opportunity to take a higher-resolution look at genomes within single cells, extending our understanding of genomic mosaicism within the brain to the level of DNA sequence, which here revealed new somatic changes to the neuronal genome. This could provide new insights into the normal as well as abnormal brain, such as occurs in Alzheimer's and Parkinson's disease or Schizophrenia," said Jerold Chun, a co-author and Professor in the Dorris Neuroscience Center at The Scripps Research Institute.

For example, the new sequencing approach identified gains or loss of single copy DNA as small as 1 million base pairs, the highest resolution to date for single-cell sequencing approaches. Recent single-cell sequencing studies have used older techniques which can only decipher DNA copy changes that are at least three to six million base pairs.

Amplification in Nano-Scale Wells

The 12 nanoliter (nL) volume microwells in which amplification takes place are some of the smallest volume wells to be used in published protocols for single-cell genome sequencing.

"By reducing amplification reaction volumes 1000-fold to nanoliter levels in thousands of microwells, we increased the effective concentration of the template genome, leading to improved amplification uniformity and reduced DNA contamination," explained Jeff Gole, the first author on the paper. Gole worked on this project as a Ph.D. student in Kun Zhang's bioengineering lab at the UC San Diego Jacobs School of Engineering. Gole is now a Scientist at Good Start Genetics in Cambridge, Mass.

Compared to the most complete previously published single E. coli genome data set, the new approach recovered 50 percent more of the E. coli genome with 3 to 13-fold less sequencing data.

"The results demonstrate that MIDAS provides a much more efficient way to assemble whole bacterial genomes from single cells without culture," the authors write in the Nature Biotechnology paper.

Multidisciplinary Research

The genomics researchers collaborated with materials science graduate student Yu-Jui (Roger) Chiu on the microfabrication required to create the arrays of microwells. Chiu is working on his Ph.D. in the lab of UC San Diego electrical engineering professor Yu-Hwa Lo, who also directs the Nano3 Labs in UC San Diego's Qualcomm Institute, where microfabrication took place.

"This project would not have succeeded without the fabrication and instrumentation support available at the Jacobs School and the Qualcomm Institute," said Zhang. "We are very excited about our initial results as well as the possibility that researchers around the world will be able to use this approach in many different contexts."

###

Prof. Kun Zhang is the PI on an NIH-funded center dedicated to the analysis and visualization of RNA transcripts - a proxy for gene activity - from individual cells within the human brain.

This project was funded by US National Institutes of Health grants R01HG004876, R01GM097253, U01MH098977 and P50HG005550, and National Science Foundation grant OCE-1046368.

A patent application has been filed, and UC San Diego is seeking commercial partners to license and develop this innovation into useful products. For information, contact:

"Massively parallel polymerase cloning and genome sequencing of single cells using nanoliter microwells," in Nature Technology by: Jeff Gole (1), Athurva Gore (1), Andrew Richards (1), Yu-Jui Chiu (2), Ho-Lim Fung (1), Diane Bushman (3), Hsin-I Chiang (1,5), Jerold Chun (3), Yu-Hwa Lo (4), Kun Zhang (1)

(1) = Department of Bioengineering, Institute for Genomic Medicine and Institute of Engineering in Medicine, University of California, San Diego

(2) = Materials Science and Engineering Program, University of California, San Diego

(3) = Dorris Neuroscience Center, Molecular and Cellular Neuroscience Department, The Scripps Research Institute

(4) = Department of Electrical and Computer Engineering, University of California, San Diego

(5) = Present address: Department of Animal Science, National Chung Hsing University

####

For more information, please click here

Contacts:
Daniel Kane

858-534-3262

Copyright © University of California - San Diego

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related News Press

News and information

Mass spectrometers with optimised hydrogen pumping March 1st, 2015

Imec Demonstrates Compact Wavelength-Division Multiplexing CMOS Silicon Photonics Transceiver March 1st, 2015

onic Present breakthrough in CMOS-based Transceivers for mm-Wave Radar Systems March 1st, 2015

Graphene Shows Promise In Eradication Of Stem Cancer Cells March 1st, 2015

Govt.-Legislation/Regulation/Funding/Policy

First detailed microscopy evidence of bacteria at the lower size limit of life: Berkeley Lab research provides comprehensive description of ultra-small bacteria February 28th, 2015

Warming up the world of superconductors: Clusters of aluminum metal atoms become superconductive at surprisingly high temperatures February 25th, 2015

SUNY Poly CNSE Researchers and Corporate Partners to Present Forty Papers at Globally Recognized Lithography Conference: SUNY Poly CNSE Research Group Awarded Both ‘Best Research Paper’ and ‘Best Research Poster’ at SPIE Advanced Lithography 2015 forum February 25th, 2015

European roadmap for graphene science and technology published February 25th, 2015

Nanomedicine

Graphene Shows Promise In Eradication Of Stem Cancer Cells March 1st, 2015

Novel Method to Determine Optical Purity of Drug Components March 1st, 2015

Untangling DNA with a droplet of water, a pipet and a polymer: With the 'rolling droplet technique,' a DNA-injected water droplet rolls like a ball over a platelet, sticking the DNA to the plate surface February 27th, 2015

Graphene shows potential as novel anti-cancer therapeutic strategy: University of Manchester scientists have used graphene to target and neutralise cancer stem cells while not harming other cells February 26th, 2015

Discoveries

Imec, Holst Centre and Renesas Present World’s Lowest Power 2.4GHz Radio Chip for Bluetooth Low Energy March 1st, 2015

Imec, Murata, and Huawei Introduce Breakthrough Solution for TX-to-RX Isolation in Reconfigurable, Multiband Front-End Modules for Mobile Phones: Electrical-Balance Duplexers Pave the Way to Integrated Solution for TX-to-RX Isolation March 1st, 2015

Imec Demonstrates Compact Wavelength-Division Multiplexing CMOS Silicon Photonics Transceiver March 1st, 2015

Graphene Shows Promise In Eradication Of Stem Cancer Cells March 1st, 2015

Announcements

Imec, Murata, and Huawei Introduce Breakthrough Solution for TX-to-RX Isolation in Reconfigurable, Multiband Front-End Modules for Mobile Phones: Electrical-Balance Duplexers Pave the Way to Integrated Solution for TX-to-RX Isolation March 1st, 2015

Imec Demonstrates Compact Wavelength-Division Multiplexing CMOS Silicon Photonics Transceiver March 1st, 2015

onic Present breakthrough in CMOS-based Transceivers for mm-Wave Radar Systems March 1st, 2015

Graphene Shows Promise In Eradication Of Stem Cancer Cells March 1st, 2015

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

Novel Method to Determine Optical Purity of Drug Components March 1st, 2015

Moving molecule writes letters: Caging of molecules allows investigation of equilibrium thermodynamics February 27th, 2015

Untangling DNA with a droplet of water, a pipet and a polymer: With the 'rolling droplet technique,' a DNA-injected water droplet rolls like a ball over a platelet, sticking the DNA to the plate surface February 27th, 2015

Graphene shows potential as novel anti-cancer therapeutic strategy: University of Manchester scientists have used graphene to target and neutralise cancer stem cells while not harming other cells February 26th, 2015

Patents/IP/Tech Transfer/Licensing

onic Present breakthrough in CMOS-based Transceivers for mm-Wave Radar Systems March 1st, 2015

New Paper-like Material Could Boost Electric Vehicle Batteries: Researchers create silicon nanofibers 100 times thinner than human hair for potential applications in batteries for electric cars and personal electronics February 20th, 2015

Nanotech Discoveries Move from Lab to Marketplace with Lintec Deal: Licensing Partnership Brings Together University Technology, New Richardson-Based Facility Directed by Alumni February 9th, 2015

Graphenea granted patent on graphene transfer February 9th, 2015

Nanobiotechnology

Untangling DNA with a droplet of water, a pipet and a polymer: With the 'rolling droplet technique,' a DNA-injected water droplet rolls like a ball over a platelet, sticking the DNA to the plate surface February 27th, 2015

Bacteria network for food: Bacteria connect to each other and exchange nutrients February 23rd, 2015

Building tailor-made DNA nanotubes step by step: New, block-by-block assembly method could pave way for applications in opto-electronics, drug delivery February 23rd, 2015

Better batteries inspired by lowly snail shells: Biological molecules can latch onto nanoscale components and lock them into position to make high performing Li-ion battery electrodes, according to new research presented at the 59th annual meeting of the Biophysical Society February 12th, 2015

NanoNews-Digest
The latest news from around the world, FREE




  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoTech-Transfer
University Technology Transfer & Patents
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More










ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project







© Copyright 1999-2015 7th Wave, Inc. All Rights Reserved PRIVACY POLICY :: CONTACT US :: STATS :: SITE MAP :: ADVERTISE