Table of contents

Focus on RNA sequencing quality control (SEQC)


In This Issue



Focus on RNA sequencing quality control (SEQC)

Honing our reading skills p845


Studies from the RNA Sequencing Quality Control (SEQC) initiative exemplify the kind of experimental groundwork needed to expand RNA-seq into a broader array of basic and translational applications.

First PD-1 inhibitor breezes across finish line pp847 - 848

Cormac Sheridan


Biotech drugs too little, too late for Ebola outbreak pp849 - 850

Stephen Strauss


Organs-on-chips Harvard spinout p849


Roche snaps up RNA-medicines firm Santaris p849


Rabbit milk Ruconest for hereditary angioedema p849


Sanofi to propel inhalable insulin Afrezza into market pp851 - 852

Jim Kling


CAR-T cell therapy gets breakthrough status p851


NCATs drug candidate attracts first buyer p851


Google Ventures launches London office p852


Small biotech steers HDAC inhibitor to clinic pp853 - 854

Mark Ratner


Around the world in a month p854


FDA pushes for control over laboratory-developed tests p855

Mark Ratner


Bioelectronics SPARC at NIH p855


First biosimilars trickle into US pathway p855


Novartis signs up for Google smart lens p856

Melanie Senior


Vitamin A Super Banana in human trials p857

Emily Waltz


RAC to finally relax gene therapy oversight p858

Asher Mullard


News Feature

Stepping into the sunshine pp859 - 862

Charles Schmidt


Is the imminent release of the database of industry's 'gifts' to doctors cause for concern or celebration? Charles Schmidt investigates.



Building a business

Building a curriculum for bioentrepreneurs pp863 - 865

Lynn Johnson Langer


How best to educate scientists about the business of biotech?


Startups on the menu: Alnylam p866



Opinion and Comment


OpenBiome remains open to serve the medical community p867

Mark Smith, Zain Kassam, Carolyn Edelstein, James Burgess & Eric Alm


Field trial of Xanthomonas wilt disease-resistant bananas in East Africa pp868 - 870

Leena Tripathi, Jaindra Nath Tripathi, Andrew Kiggundu, Sam Korie, Frank Shotkoski & Wilberforce Kateera Tushemereirwe



Scientific rigor and the art of motorcycle maintenance pp871 - 873

Marcus Munafò, Simon Noble, William J Browne, Dani Brunner, Katherine Button, Joaquim Ferreira, Peter Holmans, Douglas Langbehn, Glyn Lewis, Martin Lindquist, Kate Tilling, Eric-Jan Wagenmakers & Robi Blumenstein


The reliability of scientific research is under scrutiny. A recently convened working group proposes cultural adjustments to incentivize better research practices.

The special case of gene therapy pricing pp874 - 876

Troyen A Brennan & James M Wilson


Gene therapy companies that pursue high, one-time payments for their products risk a backlash from payors. A better solution may lie in a pay-for-performance model.




Patents or patients: who loses? pp877 - 880

Joanna Brougher & Konstantin M Linnik


The unprecedented weakening of patent rights in the United States undermines necessary incentives for the discovery and development of innovative medicines.


News and Views

Focus on RNA sequencing quality control (SEQC)

The devil in the details of RNA-seq pp882 - 884

Anton Kratz & Piero Carninci


Large-scale consortium efforts provide a thorough understanding of RNA-seq.

See also: Computational Biology by Li et al. | Computational Biology by Risso et al. | Research by SEQC/MAQC-III Consortium | Research by Li et al. | Research by Wang et al.

Focus on RNA sequencing quality control (SEQC)

Bringing RNA-seq closer to the clinic pp884 - 885

Kendall Van Keuren-Jensen, Jonathan J Keats & David W Craig


Several multicenter benchmark data sets represent valuable steps toward using RNA-seq as a diagnostic tool with clinical utility.

See also: Computational Biology by Li et al. | Computational Biology by Risso et al. | Research by SEQC/MAQC-III Consortium | Research by Li et al. | Research by Wang et al.

Research Highlights p885


Wheat rescued from fungal disease pp886 - 887

Javier Gil-Humanes & Daniel F. Voytas


Knockout of all six alleles of a gene in the large wheat genome confers resistance to powdery mildew.

See also: Research by Wang et al.

New plant species through grafting p887

Peter Hare



Computational Biology


Focus on RNA sequencing quality control (SEQC)

Detecting and correcting systematic variation in large-scale RNA sequencing data pp888 - 895

Sheng Li, Paweł P Łabaj, Paul Zumbo, Peter Sykacek, Wei Shi, Leming Shi, John Phan, Po-Yen Wu, May Wang, Charles Wang, Danielle Thierry-Mieg, Jean Thierry-Mieg, David P Kreil & Christopher E Mason


Li et al. identify the top-performing methods to improve cross-site differential gene expression analysis with RNA-seq.

See also: News and Views by Kratz & Carninci | News and Views by Van Keuren-Jensen et al.

Focus on RNA sequencing quality control (SEQC)

Normalization of RNA-seq data using factor analysis of control genes or samples pp896 - 902

Davide Risso, John Ngai, Terence P Speed & Sandrine Dudoit


Remove unwanted variation (RUV) is a new statistical method for RNA-seq data normalization that uses control genes or samples to improve differential expression analysis.

See also: News and Views by Kratz & Carninci | News and Views by Van Keuren-Jensen et al.




Focus on RNA sequencing quality control (SEQC)

A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium pp903 - 914

SEQC/MAQC-III Consortium


The Sequencing Quality Control (SEQC) consortium shows that junction discovery and differential gene expression profiling with RNA-seq can be robust but transcript-level and absolute measurements remain challenging.

See also: News and Views by Kratz & Carninci | News and Views by Van Keuren-Jensen et al.

Focus on RNA sequencing quality control (SEQC)

Multi-platform assessment of transcriptome profiling using RNA-seq in the ABRF next-generation sequencing study pp915 - 925

Sheng Li, Scott W Tighe, Charles M Nicolet, Deborah Grove, Shawn Levy, William Farmerie, Agnes Viale, Chris Wright, Peter A Schweitzer, Yuan Gao, Dewey Kim, Joe Boland, Belynda Hicks, Ryan Kim, Sagar Chhangawala, Nadereh Jafari, Nalini Raghavachari, Jorge Gandara, Natàlia Garcia-Reyero, Cynthia Hendrickson, David Roberson, Jeffrey A Rosenfeld, Todd Smith, Jason G Underwood, May Wang, Paul Zumbo, Don A Baldwin, George S Grills & Christopher E Mason


For intact RNA, gene expression profiles from rRNA-depletion and poly-A enrichment are similar. In addition, rRNA- depletion enables effective analysis of degraded RNA samples.

See also: News and Views by Kratz & Carninci | News and Views by Van Keuren-Jensen et al.

Focus on RNA sequencing quality control (SEQC)

The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance pp926 - 932

Charles Wang, Binsheng Gong, Pierre R Bushel, Jean Thierry-Mieg, Danielle Thierry-Mieg, Joshua Xu, Hong Fang, Huixiao Hong, Jie Shen, Zhenqiang Su, Joe Meehan, Xiaojin Li, Lu Yang, Haiqing Li, Paweł P Łabaj, David P Kreil, Dalila Megherbi, Stan Gaj, Florian Caiment, Joost van Delft, Jos Kleinjans, Andreas Scherer, Viswanath Devanarayan, Jian Wang, Yong Yang, Hui-Rong Qian, Lee J Lancashire, Marina Bessarabova, Yuri Nikolsky, Cesare Furlanello, Marco Chierici, Davide Albanese, Giuseppe Jurman, Samantha Riccadonna, Michele Filosi, Roberto Visintainer, Ke K Zhang, Jianying Li, Jui-Hua Hsieh, Daniel L Svoboda, James C Fuscoe, Youping Deng, Leming Shi, Richard S Paules, Scott S Auerbach & Weida Tong


A comparison of RNA-seq and microarray data from samples treated with diverse drugs highlights a dependency of cross-platform concordance on treatment effect.

See also: News and Views by Kratz & Carninci | News and Views by Van Keuren-Jensen et al.

Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification pp933 - 940

Jeffrey J Quinn, Ibrahim A Ilik, Kun Qu, Plamen Georgiev, Ci Chu, Asifa Akhtar & Howard Y Chang


Domain-specific chromatin isolation by RNA purification (dChIRP) identifies interacting partners of functional regions of long noncoding RNAs.


Generation of mouse models of myeloid malignancy with combinatorial genetic lesions using CRISPR-Cas9 genome editing pp941 - 946

Dirk Heckl, Monika S Kowalczyk, David Yudovich, Roger Belizaire, Rishi V Puram, Marie E McConkey, Anne Thielke, Jon C Aster, Aviv Regev & Benjamin L Ebert


The genetic complexity of human leukemia is modeled using the CRISPR-Cas9 system in mice.

Simultaneous editing of three homoeoalleles in hexaploid bread wheat confers heritable resistance to powdery mildew pp947 - 951

Yanpeng Wang, Xi Cheng, Qiwei Shan, Yi Zhang, Jinxing Liu, Caixia Gao & Jin-Long Qiu


TALEN-induced mutation of all homologous copies of a gene that represses resistance to an important wheat pathogen confers a trait that has eluded plant breeders for decades.

See also: News and Views by Gil-Humanes & Voytas


Erratum: HIV immunity goes direct p952


Erratum: University biotech patenting 2013 p952

Brady Huggett & Kathryn Paisner


Erratum: In Their Words p952



Corrigendum: Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype p952

Hao Yin, Wen Xue, Sidi Chen, Roman L Bogorad, Eric Benedetti, Markus Grompe, Victor Koteliansky, Phillip A Sharp, Tyler Jacks & Daniel G Anderson



Careers and Recruitment

Mobility, retention and productivity of genomics scientists in the United States pp953 - 958

Kenneth Guang-Lih Huang & Gokhan Ertug


The United States appears to have an increasingly weakening ability to attract and retain genomics scientists.


People p960



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