The shift to digital systems for the creation, transmission and storage of information has led to increasing complexity in archiving, requiring active, ongoing maintenance of the digital media. DNA is an attractive target for information storage 1 because of its capacity for high density information encoding, longevity under easily-achieved conditions 2-4 and proven track record as an information bearer. Previous DNA-based information storage approaches have encoded only trivial amounts of information 5-7 or were not amenable to scaling-up 8 , and used no robust errorcorrection and lacked examination of their cost-efficiency for large-scale information archival 9 . Here we describe a scalable method that can reliably store more information than has been handled before. We encoded computer files totalling 739 kB of hard disk storage and with an estimated Shannon information 10 of 5.2 × 10 6 bits into a DNA code, synthesised this DNA, sequenced it and reconstructed the original files with 100% accuracy. Theoretical analysis indicates that our DNA-storage scheme scales far beyond current global information volumes. These results demonstrate DNA-storage to be a realistic technology for large-scale digital archiving that may already be cost-effective for low access, multi-century-long archiving tasks. Within a decade, as costs fall rapidly under realistic scenarios for technological advances, it may be cost-effective for sub-50-year archival.Although techniques for manipulating, storing and copying large amounts of DNA have been established for many years [11][12][13] , these rely on the availability of initial copies of the DNA molecule to be processed, and one of the main challenges for practical information storage in DNA is the difficulty of synthesising long sequences of DNA de novo to an exactly-specified design. Instead, we developed an in vitro approach that represents the information being stored as a hypothetical long DNA molecule and encodes this using shorter DNA fragments. A similar approach was proposed by Church et al. 9 in a report * To whom correspondence should be addressed; goldman@ebi.ac.uk. SupplementaryInformation is provided as a number of separate files accompanying this document.Author Contributions N.G. and E.B. conceived and planned the project and devised the information encoding methods. P.B. advised on NGS protocols, prepared the DNA library and managed the sequencing process. S.C. and E.M.L. provided custom oligonucleotides. N.G. wrote the software for encoding and decoding information into/from DNA and analysed the data. N.G., E.B., C.D. and B.S. modelled the scaling properties of DNA-storage. N.G. wrote the paper with discussions and contributions from all other authors. N.G. and C.D. produced the figures.Author Information Data are available online at http://www.ebi.ac.uk/goldman-srv/DNA-storage and in the Sequence Read Archive (SRA) with accession number ERP002040 (to be confirmed). Correspondence and requests for materials should be addressed to N.G. (goldman@ebi.ac.uk). Co...

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SUMMARY Genetic interaction (GI) maps, comprising pairwise measures of how strongly the function of one gene depends on the presence of a second, have enabled the systematic exploration of gene function in microorganisms. Here, we present a two-stage strategy to construct high-density GI maps in mammalian cells. First, we use ultra-complex pooled shRNA libraries (25 shRNAs/gene) to identify high-confidence hit genes for a given phenotype and effective shRNAs. We then construct double-shRNA libraries from these to systematically measure GIs between hits. A GI map focused on ricin susceptibility broadly recapitulates known pathways and provides many unexpected insights. These include a non-canonical role for COPI, a novel protein complex (SRIC) affecting toxin clearance, a specialized role for the ribosomal protein RPS25, and functionally distinct mammalian TRAPP complexes. The ability to rapidly generate mammalian GI maps provides a potentially transformative tool for defining gene function and designing combination therapies based on synergistic pairs.

Macrophages are crucial members of the innate immune response and important regulators. The differentiation and activation of macrophages require the timely regulation of gene expression, which depends on the interaction of a variety of factors, including transcription factors and epigenetic modifications. Epigenetic changes also give macrophages the ability to switch rapidly between cellular programs, indicating the ability of epigenetic mechanisms to affect phenotype plasticity. In this review, we focus on key epigenetic events associated with macrophage fate, highlighting events related to the maintenance of tissue homeostasis, responses to different stimuli and the formation of innate immune memory. Further understanding of the epigenetic regulation of macrophages will be helpful for maintaining tissue integrity, preventing chronic inflammatory diseases and developing therapies to enhance host defense.

Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm with high morbidity and mortality. The initiating mechanism during the pathogenesis of KHE has yet to be discovered. The main pathological features of KHE are abnormal angiogenesis and lymphangiogenesis. KHEs are clinically heterogeneous and may develop into a lifethreatening thrombocytopenia and consumptive coagulopathy, known as the Kasabach-Merritt phenomenon (KMP). The heterogeneity and the highly frequent occurrence of disease-related comorbidities make the management of KHE challenging. Currently, there are no medications approved by the FDA for the treatment of KHE. Multiple treatment regimens have been used with varying success, and new clinical trials are in progress. In severe patients, multiple agents with variable adjuvant therapies are given in sequence or in combination. Recent studies have demonstrated a satisfactory efficacy of sirolimus, an inhibitor of mammalian target of rapamycin, in the treatment of KHE. Novel targeted treatments based on a better understanding of the pathogenesis of KHE are needed to maximize patient outcomes and quality of life. This review summarizes the epidemiology, etiology, pathophysiology, clinical features, diagnosis and treatments of KHE. Recent new concepts and future perspectives for KHE will also be discussed.