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In the emerging field of laser-driven inertial confinement fusion, Joule heating generated via electromagnetic heating of the metal frame is a critical issue. However, there are few reported models explaining thermal damage to the aluminum alloy. The aim of this study was to build a coupled model for electromagnetic radiation and heat conversion of an ultrashort laser pulse on an aluminum alloy based on Ohm's law. Additionally, the application SiO2 films on aluminum alloy to improve the laser-induced damage threshold (LIDT) were simulated, and the effects of metal impurities in the aluminum alloy were analyzed. A model examining the relation between electromagnetic radiation and heat for a nanosecond laser irradiating an aluminum alloy was developed using a coupled model equation. The results obtained using the finite difference time domain (FDTD) algorithm can provide a theoretical basis for future improvement of the aluminum alloy LIDT.

To assess the clinical performance of an expanded noninvasive prenatal screening (NIPS) test (“NIPS-Plus”) for detection of both aneuploidy and genome-wide microdeletion/microduplication syndromes (MMS). A total of 94,085 women with a singleton pregnancy were prospectively enrolled in the study. The cell-free plasma DNA was directly sequenced without intermediate amplification and fetal abnormalities identified using an improved copy-number variation (CNV) calling algorithm. A total of 1128 pregnancies (1.2%) were scored positive for clinically significant fetal chromosome abnormalities. This comprised 965 aneuploidies (1.026%) and 163 (0.174%) MMS. From follow-up tests, the positive predictive values (PPVs) for T21, T18, T13, rare trisomies, and sex chromosome aneuploidies were calculated as 95%, 82%, 46%, 29%, and 47%, respectively. For known MMS (n = 32), PPVs were 93% (DiGeorge), 68% (22q11.22 microduplication), 75% (Prader–Willi/Angleman), and 50% (Cri du Chat). For the remaining genome-wide MMS (n = 88), combined PPVs were 32% (CNVs ≥10 Mb) and 19% (CNVs

Nanocomposite multilayer TiBN coatings were prepared on Si (100) and 9Cr18Mo substrates using TiBN composite cathode plasma immersion ion implantation and deposition technique (PIIID). Synthesis of TiBN composite cathodes was conducted by powder metallurgy technology and the content of hexagonal boron nitride (h-BN) was changed from 8% to 40% (mass fraction). The as-deposited coatings were characterized by energy dispersive spectrometer (EDS), grazing incidence X-ray diffraction (GIXRD), Fourier Transform Infrared Spectroscopy (FTIR) and high resolution transmission electron microcopy (HRTEM). EDS results show that the B content of the coatings was varied from 3.71% to 13.84% (molar fraction) when the composition of the h-BN in the composited cathodes was changed from 8 % to 40% (mass fraction). GIXRD results reveal that the TiBN coatings with a B content of 8% has the main diffraction peak of TiN (200), (220) and (311), and these peaks disappear when the B content is increased. FTIR analysis of the multilayer coatings showed the presence of h-BN in all coatings. TEM images reveal that all coatings have the characteristics of self-forming nanocomposite multilayers, where the nanocomposites are composed of face-centered cubic TiN or h-BN nanocrystalline embedded in amorphous matrix. The tribological tests reveal that the TiBN coatings exhibit a marked decrease of coefficient at room temperature (~0.25). The improved properties were found to be derived from the comprehensiveness of the self-forming multilayers structure and the h-BN solid lubrication effects in the coatings.

Detailed characterization of chromosomal abnormalities, a common cause for congenital abnormalities and pregnancy loss, is critical for elucidating genes for human fetal development. Here, 2186 product of conception (POC) samples were tested for copy number variations (CNVs) at two clinical diagnostic centers using whole genome sequencing and high-resolution chromosomal microarray analysis. We developed a new gene discovery approach to predict potential developmental genes and identified 275 candidate genes from CNVs detected from both datasets. Based on Mouse Genome Informatics (MGI) and Zebrafish model organism database (ZFIN), 75% of identified genes could lead to developmental defects when mutated. Genes involved in embryonic development, gene transcription and regulation of biological processes were significantly enriched. Especially, transcription factors and gene families sharing specific protein domains predominated, which included known developmental genes such as HOX, NKX homeodomain genes and helix-loop-helix containing HAND2, NEUROG2 and NEUROD1 as well as potential novel developmental genes. We observed that developmental genes were denser in certain chromosomal regions, enabling identification of 31 potential genomic loci with clustered genes associated with development.

Whole-genome sequencing (WGS) allows for a comprehensive view of the sequence of the human genome. We present and apply integrated methodologic steps for interrogating WGS data to characterize the genetic architecture of 10 heart- and blood-related traits in a sample of 1,860 African Americans. In order to evaluate the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests of rare variation across the entire genomic landscape using a sliding window, complemented by an annotation-based assessment of the genome using predefined regulatory elements and within the first intron of all genes. These tests were performed treating all variants equally as well as with individual variants weighted by a measure of predicted functional consequence. Significant findings were assessed in 1,705 individuals of European ancestry. After these steps, we identified and replicated components of the genomic landscape significantly associated with heart- and blood-related traits. For two traits, lipoprotein(a) levels and neutrophil count, aggregate tests of low-frequency and rare variation were significantly associated across multiple motifs. For a third trait, cardiac troponin T, investigation of regulatory domains identified a locus on chromosome 9. These practical approaches for WGS analysis led to the identification of informative genomic regions and also showed that defined non-coding regions, such as first introns of genes and regulatory domains, are associated with important risk factor phenotypes. This study illustrates the tractable nature of WGS data and outlines an approach for characterizing the genetic architecture of complex traits.

Thermal problems are huge challenges for solid state lasers that are interested in high output power, cooling of the nonlinear optics is insufficient to completely solve the problem of thermally induced stress, as residual thermal stress remains after cooling, which is first proposed, to the best of our knowledge. In this paper a comprehensive model incorporating principles of thermodynamics, mechanics and optics is proposed, and it is used to study the residual thermal stress of a mounted KDP crystal after cooling process from mechanical perspective, along with the effects of the residual thermal stress on the second harmonic generation (SHG) efficiency of a high-average-power laser. Effects of the structural parameters of the mounting configuration of the KDP crystal on the residual thermal stress are characterized, as well as the SHG efficiency. The numerical results demonstrate the feasibility of solving the problems of residual thermal stress from the perspective on structural design of mounting configuration.

The microstructural evolution process of face-centered cubic Cu-30 wt%Zn, which has very low stacking fault (SF) energy of only 14 mJ/m 2 , processed by high-pressure torsion, was investigated using transmission electron microscopy. Results reveal that deformation SFs/twin boundaries and cell blocks play the key role in the grain refinement process from ultrafine grains to nano grains. Equiaxed coarse grains with grain sizes of several microns were refined to ultrafine grains through the formation of high density of SFs, twins and cell blocks. With the accumulation of high density of dislocations at SF/twin boundaries, the emission of secondary SFs/twins further refined grains and transformed ultrafine grains into equiaxed grains with grain size of several tens nanometers. The observed grain refinement mechanism is significantly different from those of materials with medium to high SF energies in which full dislocation activities play a key role for grain refinement.

Understanding the evolution of disease-associated mutations is fundamental to analyze pathogenetics of diseases. Mutation, recombination (by GC-biased gene conversion, gBGC), and selection have been known to shape the evolution of disease-associated mutations, but how these evolutionary forces work together is still an open question. In this study, we analyzed several human large-scale datasets (1000 Genomes, ESP6500, ExAC and ClinVar), and found that base-biased mutagenesis generates more GC→AT than AT→GC mutations, while gBGC promotes the fixation of AT→GC mutations to balance the impact of base-biased mutation on genome. Due to this effect of gBGC, purifying selection removes more deleterious AT→GC mutations than GC→AT from population, but many high-frequency (fixed and nearly fixed) deleterious AT→GC mutations are remained possibly due to high genetic load. As a special subset, disease-associated mutations follow this evolutionary rule, in which disease-associated GC→AT mutations are more enriched in rare mutations compared with AT→GC, while disease-associated AT→GC are more enriched in mutations with high frequency. Thus, we presented a base-biased evolutionary framework that explains the base-biased generation and accumulation of disease-associated mutations in human populations.

Aluminum alloys are widely applied in optical turrets after coating and super-finishing. Gold films prepared on aluminum alloy substrates via electron beam (e-beam) evaporation are considered to be effective way to realize close to total reflection of incident light. Here, we investigated the optimization of the reflectivity parameters of e-beam evaporated gold films; then, the influence of different deposition parameters on the surface quality, adhesive force and reflectivity (incident light in the 650–1700 nm range) of the film at −20, 25 and 60°C were systematically studied. The results demonstrated that the reflectivity and adhesion of the gold films both increased after high temperature holding and decreased slightly after low temperature holding. However, the surface morphology of the gold film did not change substantially. After holding at 60 and −20°C, the adhesive force decreased, which indicated that the adhesion strength between the reflective membrane and the substrate decreased.

Introduction: The metabolome is a collection of small molecules in a biologic sample, and may serve as biomarkers or predictors of heart disease. Whole genome sequence analysis offers the opportunity to investigate rare and low-frequency annotated variants across the human genome. We used whole genome sequence analysis to characterize the genetic architecture of the serum metabolome. Methods: Whole genome sequencing and measurement (chromotagraphy and mass spectroscopy) of 245 serum metabolites were done in 1,458 European Americans and 1,679 African Americans from the Atherosclerosis Risk in Communities (ARIC) study, and these data were used to perform a trans-ethnic meta-analysis. Common variants (MAF>5%) were analyzed individually using an additive genetic model. Rare and low-frequency protein-altering variants (MAF≤5%) were aggregated by genes. In order to determine the contribution of regulatory and non-protein coding regions of the genome, we conducted aggregate tests across the entire genome using a 4kb sliding window as well as in predefined regulatory elements, which includs enhancers, promoter, and 3’ and 5’ untranslated region of a gene. Results: We identified 119 significant associations between genetic variants and metabolite levels (significance threshold p-10 for single variants, p-10 for aggregate tests), of which 49 were novel, including genes involved in known Mendelian conditions, protein biological processes, and disease related pathways. Six genes ( DMGDH, AGA, ACY1, PRODH, DDC and CPS1 ) causing rare inborn errors of metabolism were associated with amino acid levels in the general population. A predicated regulatory variant in the AGA gene, encoding a protein involved in asparagine generation, was associated with serum asparagine levels independent of any coding variants in this gene. Seven genes ( ABCC2, PKD2L1, SLC10A1, FDX1, CYP3A43, UGT2B15 and SULT2A1 ) related to lipid-related metabolite levels were identified, whose gene products are involved in secretion, channeling and transportation. Analysis of regulatory regions unraveled associations between three steroid lipids and a member of the cytochrome P450 family, CYP3A43 . Five genes within the kinin-kallikrein pathway were identified to be related to small peptide levels, including KLKB1 , KNG1 , F12 , ACE and CPN1 . Variants in CPN1 , which is known to bind to fibrinogen, were associated with DSGEGDFXAEGGGVR, a peptide which is produced during fibrinogen to fibrin conversion. Conclusion: This study outlines an approach to characterize the genetic architecture of the human serum metabolome and shows that sequence variants affect multiple human metabolites. Using the principle of Mendelian randomization, the next step is to determine whether any of these metabolites are in causal pathways to disease.

In current work we perform molecular dynamics simulations to investigate the growth of Al thin film on Cu substrate through physical vapor deposition. The effects of incident angle on the morphology and the formed internal microstructures of Al thin films are emphasized. Simulation results show that Al thin films grow in the epitaxy growth mode of layer-by-layer fashion under incident energy of 0.1 eV. Further analysis of the internal microstructures demonstrates the formation of twin boundaries in Al thin films. It is found that the morphology of the island-like clusters formed in Al thin films varies significantly upon incident angle. The compositions of atoms of different lattice structures strongly depend on incident angle, which consequently affects the propensity of different internal microstructures formed in Al thin films.

The radiation force of a high-energy laser caused by reflection at the input surface of a mounted KHsub2/subPOsub4/sub(KDP) crystal is studied, along with its effects on the second-harmonic generation (SHG) efficiency of the laser beam. A comprehensive model incorporating principles of momentum transfer, mechanics, and optics is proposed, taking advantage of which, the mechanical stress within the KDP crystal that is caused by the radiation force, and the SHG efficiency that is affected by the stress are successively studied. Moreover, the effects of the intensity of the laser beam on the radiation force, the stress, and the SHG efficiency are determined, respectively. It demonstrates that a high-energy laser beam causes macroscopic radiation force and further contributes negative effects to SHG efficiency.

Mechanical and tribological properties of multilayers with nanometer thickness are strongly affected by interfaces formed due to mismatch of lattice parameters. In this study, molecular dynamics (MD) simulations of nanoindentation and following nanoscratching processes are performed to investigate the mechanical and tribological properties of Ni/Al multilayers with semi-coherent interface. The results show that the indentation hardness of Ni/Al multilayers is larger than pure Ni thin film, and the significant strength of Ni/Al multilayers is caused by the semi-coherent interface which acts as a barrier to glide of dislocations during nanoindentation process. The confinement of plastic deformation by the interface during nanoscratching on Ni/Al multilayers leads to smaller friction coefficient than pure Ni thin film. Dislocation evolution, interaction between gliding dislocations and interface, variations of indentation hardness and friction coefficient are studied.

In this paper we report molecular dynamics based atomistic simulations of deposition process of Al atoms onto Cu substrate and following nanoindentation process on that nanostructured material. Effects of incident energy on the morphology of deposited thin film and mechanical property of this nanostructured material are emphasized. The results reveal that the morphology of growing film is layer-by-layer-like at incident energy of 0.1–10 eV. The epitaxy mode of film growth is observed at incident energy below 1 eV, but film-mixing mode commences when incident energy increase to 10 eV accompanying with increased disorder of film structure, which improves quality of deposited thin film. Following indentation studies indicate deposited thin films pose lower stiffness than single crystal Al due to considerable amount of defects existed in them, but Cu substrate is strengthened by the interface generated from lattice mismatch between deposited Al thin film and Cu substrate.

Historical episodes of natural selection can skew the frequencies of genetic variants, leaving a signature that can persist for many tens or even hundreds of thousands of years. However, formal tests for selection based on allele frequency skew require strong assumptions about demographic history and mutation, which are rarely well understood. Here, we develop an empirical approach to test for signals of selection that compares patterns of genetic variation at a candidate locus with matched random regions of the genome collected in the same way. We apply this approach to four genes that have been implicated in syndromes of impaired neurological development, comparing the pattern of variation in our re-sequencing data with a large-scale, genomic data set that provides an empirical null distribution. We confirm a previously reported signal at FOXP2, and find a novel signal of selection centered at AHI1, a gene that is involved in motor and behavior abnormalities. The locus is marked by many high frequency derived alleles in non-Africans that are of low frequency in Africans, suggesting that selection at this or a closely neighboring gene occurred in the ancestral population of non-Africans. Our study also provides a prototype for how empirical scans for ancient selection can be carried out once many genomes are sequenced.

Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms (SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution. © 2005 Nature Publishing Group., link_to_OA_fulltext

Background Next-generation DNA sequencing is opening new avenues for genetic association studies in common diseases that, like deep vein thrombosis (DVT), have a strong genetic predisposition still largely unexplained by currently identified risk variants. In order to develop sequencing and analytical pipelines for the application of next-generation sequencing to complex diseases, we conducted a pilot study sequencing the coding area of 186 hemostatic/proinflammatory genes in 10 Italian cases of idiopathic DVT and 12 healthy controls. Results A molecular-barcoding strategy was used to multiplex DNA target capture and sequencing, while retaining individual sequence information. Genomic libraries with barcode sequence-tags were pooled (in pools of 8 or 16 samples) and enriched for target DNA sequences. Sequencing was performed on ABI SOLiD-4 platforms. We produced > 12 gigabases of raw sequence data to sequence at high coverage (average: 42X) the 700-kilobase target area in 22 individuals. A total of 1876 high-quality genetic variants were identified (1778 single nucleotide substitutions and 98 insertions/deletions). Annotation on databases of genetic variation and human disease mutations revealed several novel, potentially deleterious mutations. We tested 576 common variants in a case-control association analysis, carrying the top-5 associations over to replication in up to 719 DVT cases and 719 controls. We also conducted an analysis of the burden of nonsynonymous variants in coagulation factor and anticoagulant genes. We found an excess of rare missense mutations in anticoagulant genes in DVT cases compared to controls and an association for a missense polymorphism of FGA (rs6050; p = 1.9 × 10-5, OR 1.45; 95% CI, 1.22-1.72; after replication in > 1400 individuals). Conclusions We implemented a barcode-based strategy to efficiently multiplex sequencing of hundreds of candidate genes in several individuals. In the relatively small dataset of our pilot study we were able to identify bona fide associations with DVT. Our study illustrates the potential of next-generation sequencing for the discovery of genetic variation predisposing to complex diseases.

Background Whole exome capture sequencing allows researchers to cost-effectively sequence the coding regions of the genome. Although the exome capture sequencing methods have become routine and well established, there is currently a lack of tools specialized for variant calling in this type of data. Results Using statistical models trained on validated whole-exome capture sequencing data, the Atlas2 Suite is an integrative variant analysis pipeline optimized for variant discovery on all three of the widely used next generation sequencing platforms (SOLiD, Illumina, and Roche 454). The suite employs logistic regression models in conjunction with user-adjustable cutoffs to accurately separate true SNPs and INDELs from sequencing and mapping errors with high sensitivity (96.7%). Conclusion We have implemented the Atlas2 Suite and applied it to 92 whole exome samples from the 1000 Genomes Project. The Atlas2 Suite is available for download at http://sourceforge.net/projects/atlas2/. In addition to a command line version, the suite has been integrated into the Genboree Workbench, allowing biomedical scientists with minimal informatics expertise to remotely call, view, and further analyze variants through a simple web interface. The existing genomic databases displayed via the Genboree browser also streamline the process from variant discovery to functional genomics analysis, resulting in an off-the-shelf toolkit for the broader community.

We surveyed 16 subjects with the clinical diagnosis of Noonan Syndrome (NS1) from 12 families and their relevant family members for mutations in PTPN11/SHP2 using direct DNA sequencing. We found three different mutations among five families. Two unrelated subjects shared the same de novo missense substitution in exon 13 (S502T); an additional two unrelated families had a mutation in exon 3 (Y63C); and one subject had the amino acid substitution Y62D, also in exon 3. None of the three mutations were present in ethnically matched controls. In the mature protein model, the exon 3 mutants and the exon 13 mutant amino acids cluster at the interface between the N' SH2 domain and the phosphatase catalytic domain. Six of eight subjects with PTPN11/SHP2 mutations had pulmonary valve stenosis while no mutations were identified in those subjects (N = 4) with hypertrophic cardiomyopathy. An additional four subjects with possible Noonan syndrome were evaluated, but no mutations in PTPN11/SHP2 were identified. These results confirm that mutations in PTPN11/SHP2 underlie a common form of Noonan syndrome, and that the disease exhibits both allelic and locus heterogeneity. The observation of recurrent mutations supports the hypothesis that a special class of gain-of-function mutations in SHP2 give rise to Noonan syndrome.

Admixture mapping is an economical and powerful approach for localizing disease genes in populations of recently mixed ancestry and has proven successful in African Americans. The method holds equal promise for Latinos, who typically inherit a mix of European, Native American, and African ancestry. However, admixture mapping in Latinos has not been practical because of the lack of a map of ancestry-informative markers validated in Native American and other populations. To address this, we screened multiple databases, containing millions of markers, to identify 4,186 markers that were putatively informative for determining the ancestry of chromosomal segments in Latino populations. We experimentally validated each of these markers in at least 232 new Latino, European, Native American, and African samples, and we selected a subset of 1,649 markers to form an admixture map. An advantage of our strategy is that we focused our map on markers distinguishing Native American from other ancestries and restricted it to markers with very similar frequencies in Europeans and Africans, which decreased the number of markers needed and minimized the possibility of false disease associations. We evaluated the effectiveness of our map for localizing disease genes in four Latino populations from both North and South America. COL0006723

Background Generation of long (>5 Kb) DNA sequencing reads provides an approach for interrogation of complex regions in the human genome. Currently, large-insert whole genome sequencing (WGS) technologies from Pacific Biosciences (PacBio) enable analysis of chromosomal structural variations (SVs), but the cost to achieve the required sequence coverage across the entire human genome is high. Results We developed a method (termed PacBio-LITS) that combines oligonucleotide-based DNA target-capture enrichment technologies with PacBio large-insert library preparation to facilitate SV studies at specific chromosomal regions. PacBio-LITS provides deep sequence coverage at the specified sites at substantially reduced cost compared with PacBio WGS. The efficacy of PacBio-LITS is illustrated by delineating the breakpoint junctions of low copy repeat (LCR)-associated complex structural rearrangements on chr17p11.2 in patients diagnosed with Potocki–Lupski syndrome (PTLS; MIM#610883). We successfully identified previously determined breakpoint junctions in three PTLS cases, and also were able to discover novel junctions in repetitive sequences, including LCR-mediated breakpoints. The new information has enabled us to propose mechanisms for formation of these structural variants. Conclusions The new method leverages the cost efficiency of targeted capture-sequencing as well as the mappability and scaffolding capabilities of long sequencing reads generated by the PacBio platform. It is therefore suitable for studying complex SVs, especially those involving LCRs, inversions, and the generation of chimeric Alu elements at the breakpoints. Other genomic research applications, such as haplotype phasing and small insertion and deletion validation could also benefit from this technology. Electronic supplementary material The online version of this article (doi:10.1186/s12864-015-1370-2) contains supplementary material, which is available to authorized users.

Background Rhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies. Results We used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease. Conclusions Resequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease.

Background Gene expression is one of the most relevant biological processes of living cells. Due to the relative small population sizes, it is predicted that human gene sequences are not strongly influenced by selection towards expression efficiency. One of the major problems in estimating to what extent gene characteristics can be selected to maximize expression efficiency is the wide variation that exists in RNA and protein levels among physiological states and different tissues. Analyses of datasets of stably expressed genes (i.e. with consistent expression between physiological states and tissues) would provide more accurate and reliable measurements of associations between variations of a specific gene characteristic and expression, and how distinct gene features work to optimize gene expression. Results Using a dataset of human genes with consistent expression between physiological states we selected gene sequence signatures related to translation that can predict about 42% of mRNA variation. The prediction can be increased to 51% when selecting genes that are stably expressed in more than 1 tissue. These genes are enriched for translation and ribosome biosynthesis processes and have higher translation efficiency scores, smaller coding sequences and 3′ UTR sizes and lower folding energies when compared to other datasets. Additionally, the amino acid frequencies weighted by expression showed higher correlations with isoacceptor tRNA gene copy number, and smaller absolute correlation values with biosynthetic costs. Conclusion Our results indicate that human gene sequence characteristics related to transcription and translation processes can co-evolve in an integrated manner in order to optimize gene expression.

Background Massively parallel DNA sequencing generates staggering amounts of data. Decreasing cost, increasing throughput, and improved annotation have expanded the diversity of genomics applications in research and clinical practice. This expanding scale creates analytical challenges: accommodating peak compute demand, coordinating secure access for multiple analysts, and sharing validated tools and results. Results To address these challenges, we have developed the Mercury analysis pipeline and deployed it in local hardware and the Amazon Web Services cloud via the DNAnexus platform. Mercury is an automated, flexible, and extensible analysis workflow that provides accurate and reproducible genomic results at scales ranging from individuals to large cohorts. Conclusions By taking advantage of cloud computing and with Mercury implemented on the DNAnexus platform, we have demonstrated a powerful combination of a robust and fully validated software pipeline and a scalable computational resource that, to date, we have applied to more than 10,000 whole genome and whole exome samples.