In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Question: Containment of the SARS coronavirus (SCV) outbreak was accompanied by the rapid characterization of this new pathogen's genome sequence in 2003, encouraging the development of anti-SCV therapeutics using short interfering RNA (siRNA) inhibitors. A pair of siRNA duplexes identified as potent SCV inhibitors in vitro was evaluated for in vivo efficacy and safety in a rhesus macaque SARS model using intranasal administration with clinical viable delivery carrier in three dosing regimens. Observations of SCV-induced SARS-like symptoms, measurements of SCV RNA presence in the respiratory tract, microscopic inspections of lung histopathology, and immunohistochemistry sections from 21 tested macaques consistently demonstrated siRNA-mediated anti-SCV activity. The prophylactic and therapeutic efficacies resulted in relief of animals from SCV infectioninduced fever, diminished SCV in upper airway and lung alveoli, and milder acute diffuse alveoli damage (DAD). The dosages of siRNA used, 10 to 40 mg/kg, did not show any sign of siRNA-induced toxicity. These results support that a clinical investigation of this anti-SARS siRNA therapeutic agent is warranted. The study also illustrates the capability of siRNA to enable a massive reduction in development time for novel targeted therapeutic agents. We detail a representative example of large-mammal siRNA use.

Answer: Application of siRNA Against SARS in the Rhesus Macaque Model


Question: The Collaborative Cross (CC) is a multiparent panel of recombinant inbred (RI) mouse strains derived from eight founder laboratory strains. RI panels are popular because of their long-term genetic stability, which enhances reproducibility and integration of data collected across time and conditions. Characterization of their genomes can be a community effort, reducing the burden on individual users. Here we present the genomes of the CC strains using two complementary approaches as a resource to improve power and interpretation of genetic experiments. Our study also provides a cautionary tale regarding the limitations imposed by such basic biological processes as mutation and selection. A distinct advantage of inbred panels is that genotyping only needs to be performed on the panel, not on each individual mouse. The initial CC genome data were haplotype reconstructions based on dense genotyping of the most recent common ancestors (MRCAs) of each strain followed by imputation from the genome sequence of the corresponding founder inbred strain. The MRCA resource captured segregating regions in strains that were not fully inbred, but it had limited resolution in the transition regions between founder haplotypes, and there was uncertainty about founder assignment in regions of limited diversity. Here we report the whole genome sequence of 69 CC strains generated by paired-end short reads at 303 coverage of a single male per strain. Sequencing leads to a substantial improvement in the fine structure and completeness of the genomes of the CC. Both MRCAs and sequenced samples show a significant reduction in the genome-wide haplotype frequencies from two wild-derived strains, CAST/EiJ and PWK/PhJ. In addition, analysis of the evolution of the patterns of heterozygosity indicates that selection against three wild-derived founder strains played a significant role in shaping the genomes of the CC. The sequencing resource provides the first description of tens of thousands of new genetic variants introduced by mutation and drift in the CC genomes. We estimate that new SNP mutations are accumulating in each CC strain at a rate of 2.4 6 0.4 per gigabase per generation. The fixation of new mutations by genetic drift has introduced thousands of new variants into the CC strains. The majority of these mutations are novel compared to currently sequenced laboratory stocks and wild mice, and some are predicted to alter gene function. Approximately one-third of the CC inbred strains have acquired large deletions (.10 kb) many of which overlap known coding genes and functional elements. The sequence of these mice is a critical resource to CC users, increases threefold the number of mouse inbred strain genomes available publicly, and provides insight into the effect of mutation and drift on common resources.

Answer: Genomes of the Mouse Collaborative Cross


Question: Identification and discovery of viruses using next-generation sequencing technology is a fastdeveloping area with potential wide application in clinical diagnostics, public health monitoring and novel virus discovery. However, tremendous sequence data from NGS study has posed great challenge both in accuracy and velocity for application of NGS study. Here we describe VIP ("Virus Identification Pipeline"), a one-touch computational pipeline for virus identification and discovery from metagenomic NGS data. VIP performs the following steps to achieve its goal: (i) map and filter out background-related reads, (ii) extensive classification of reads on the basis of nucleotide and remote amino acid homology, (iii) multiple k-mer based de novo assembly and phylogenetic analysis to provide evolutionary insight. We validated the feasibility and veracity of this pipeline with sequencing results of various types of clinical samples and public datasets. VIP has also contributed to timely virus diagnosis (~10 min) in acutely ill patients, demonstrating its potential in the performance of unbiased NGS-based clinical studies with demand of short turnaround time. VIP is released under GPLv3 and is available for free download at: https://github.com/keylabivdc/VIP. The world contains a high diversity of human viral pathogens. There are approximately 300 recognized viral pathogen species, and additional species continue to be discovered. The identification of viral pathogens has a tremendous impact on infectious diseases, virology and public health. Nearly all of the outbreaks of public health issues over the last decade have been caused by viruses, including Severe Acute Respiratory Syndrome (SARS) coronavirus 1 , 2009 pandemic influenza H1N1 2 , H7N9 avian influenza viruses 3 and the recently described Ebola virus in West Africa 4 . Traditional diagnostic methods for viruses, such as cell culture, serodiagnosis, or nucleic acid-based testing are narrow in scope and require a priori knowledge of the potential infectious agents 5,6 . Accurate diagnosis and timely treatment for the infection dramatically reduced the risk of continued transmission and mortality in hospitalized patients 7 . Wild interest in comprehensive detection of these newly emerging and re-emerging viruses from clinical samples highlight the need for rapid, broad-spectrum diagnostic assays. Shotgun metagenomic sequencing of clinical samples for viral pathogen identification provides a promising alternative solution. Although metagenomics is typically applied to understanding genomic diversity from environment samples, this methodology has also revolutionized virology with comprehensive applications, including viral pathogen identification of infectious disease in clinical laboratories 8 and virus discovery in acute and chronic illnesses of unknown origin 9 . Many novel viruses have been discovered using popular next generation sequencing (NGS) platforms such as pyrosequencing (454 Roche), semiconductor sequencing (Life Technology) and illumina dye sequencing (Illumina) 10-12 . Achievements obtained by viral metagenomics show significant advantages over traditional methods of identifying a viral pathogen, including no need of sequence information for that pathogen, identifying multiple pathogens in a single assay and eliminating the need for time-consuming culturing or antibody laboratory tests. A key feature of latest NGS platforms is their speed. It takes minimum turnaround times about 8 hours for sequencing 13 . Thus, it is critical that subsequent computational handling of the large amount of sequence

Answer:
VIP: an integrated pipeline for metagenomics of virus identification and discovery OPEN