Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.

Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer and has very few mutations that are shared between different patients. To better understand the intratumoral genetics underlying mutations of ccRCC, we carried out single-cell exome sequencing on a ccRCC tumor and its adjacent kidney tissue. Our data indicate that this tumor was unlikely to have resulted from mutations in VHL and PBRM1. Quantitative population genetic analysis indicates that the tumor did not contain any significant clonal subpopulations and also showed that mutations that had different allele frequencies within the population also had different mutation spectrums. Analyses of these data allowed us to delineate a detailed intratumoral genetic landscape at a single-cell level. Our pilot study demonstrates that ccRCC may be more genetically complex than previously thought and provides information that can lead to new ways to investigate individual tumors, with the aim of developing more effective cellular targeted therapies.

The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A viruses. We present the duck genome sequence and perform deep transcriptome analyses to investigate immune-related genes. Our data indicate that the duck possesses a contractive immune gene repertoire, as in chicken and zebra finch, and this repertoire has been shaped through lineage-specific duplications. We identify genes that are responsive to influenza A viruses using the lung transcriptomes of control ducks and ones that were infected with either a highly pathogenic (A/duck/Hubei/49/05) or a weakly pathogenic (A/goose/Hubei/65/05) H5N1 virus. Further, we show how the duck’s defense mechanisms against influenza infection have been optimized through the diversification of its β-defensin and butyrophilin-like repertoires. These analyses, in combination with the genomic and transcriptomic data, provide a resource for characterizing the interaction between host and influenza viruses.

We are delighted to announce the launch of GigaScience, an online open-access journal that focuses on research using or producing large datasets in all areas of biological and biomedical sciences. GigaScience is a new type of journal that provides standard scientific publishing linked directly to a database that hosts all the relevant data. The primary goals for the journal, detailed in this editorial, are to promote more rapid data release, broader use and reuse of data, improved reproducibility of results, and direct, easy access between analyses and their data. Direct and permanent connections of scientific analyses and their data (achieved by assigning all hosted data a citable DOI) will enable better analysis and deeper interpretation of the data in the future.

Ras proteins are post-translationally modified by farnesylation. In the present investigation, we identified an activity in crude soluble extracts Farnesylation of Ras proteins (7-9) occurs as part of a series of C-terminal modifications needed for membrane association, including removal of three C-terminal amino acids (10, 11) and carboxyl methylation of the C-terminal cysteine (12). These modifications take place at a conserved sequence, Cys-Ali-Ali-Xaa (Ali is an aliphatic amino acid and Xaa is the unspecified C-terminal amino acid), which is termed a "CAAX" box (13). Although it appears likely that farnesylation occurs prior to amino acid removal and methylation, the order of these events has not been established.Yeast mutants defective in the processing of Ras proteins have been isolated. The dprl (14) and ram (15) mutants were independently isolated but were shown to be allelic. (This mutant will be called dprl/raml hereafter). Nonmodified Ras proteins accumulate in the mutant strains (14-16), suggesting that an early step that includes farnesylation is blocked. The mutant strains are temperature-sensitive for growth and show reduced mating efficiency. The effect on mating is severe in MATa cells, since the processing of the a-factor mating peptide is blocked (14,15). The processing of Ras proteins is also blocked in hmgl hmg2 double mutants (9). These mutations abolish 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, thus affecting the production of farnesyl pyrophosphate, which is needed for the farnesylation of Ras proteins.We have detected an activity in crude soluble extracts of yeast cells that catalyzes the farnesylation of yeast RAS2 protein. This activity is deficient in dprl/raml mutant strains. We further report the isolation of a mutation in a second gene, termed ram2, which also causes a defect in the farnesylation of Ras proteins. The availability of mutants affecting Ras processing points to the usefulness of the yeast system in analyses of protein farnesylation.