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1.  Toward clinical genomics in everyday medicine: perspectives and recommendations 
Precision or personalized medicine through clinical genome and exome sequencing has been described by some as a revolution that could transform healthcare delivery, yet it is currently used in only a small fraction of patients, principally for the diagnosis of suspected Mendelian conditions and for targeting cancer treatments. Given the burden of illness in our society, it is of interest to ask how clinical genome and exome sequencing can be constructively integrated more broadly into the routine practice of medicine for the betterment of public health. In November 2014, 46 experts from academia, industry, policy and patient advocacy gathered in a conference sponsored by Illumina, Inc. to discuss this question, share viewpoints and propose recommendations. This perspective summarizes that work and identifies some of the obstacles and opportunities that must be considered in translating advances in genomics more widely into the practice of medicine.
PMCID: PMC4841021  PMID: 26810587
Personalized medicine; precision medicine; clinical genomics; practice standards; genomic data; exome; genome; sequencing; genetic testing
2.  Assessing the Genetics Content in the Next Generation Science Standards 
PLoS ONE  2015;10(7):e0132742.
Science standards have a long history in the United States and currently form the backbone of efforts to improve primary and secondary education in science, technology, engineering, and math (STEM). Although there has been much political controversy over the influence of standards on teacher autonomy and student performance, little light has been shed on how well standards cover science content. We assessed the coverage of genetics content in the Next Generation Science Standards (NGSS) using a consensus list of American Society of Human Genetics (ASHG) core concepts. We also compared the NGSS against state science standards. Our goals were to assess the potential of the new standards to support genetic literacy and to determine if they improve the coverage of genetics concepts relative to state standards. We found that expert reviewers cannot identify ASHG core concepts within the new standards with high reliability, suggesting that the scope of content addressed by the standards may be inconsistently interpreted. Given results that indicate that the disciplinary core ideas (DCIs) included in the NGSS documents produced by Achieve, Inc. clarify the content covered by the standards statements themselves, we recommend that the NGSS standards statements always be viewed alongside their supporting disciplinary core ideas. In addition, gaps exist in the coverage of essential genetics concepts, most worryingly concepts dealing with patterns of inheritance, both Mendelian and complex. Finally, state standards vary widely in their coverage of genetics concepts when compared with the NGSS. On average, however, the NGSS support genetic literacy better than extant state standards.
PMCID: PMC4519196  PMID: 26222583
3.  Analysis of ThiC Variants in the Context of the Metabolic Network of Salmonella enterica 
Journal of Bacteriology  2012;194(22):6088-6095.
In bacteria, the 4-amino-hydroxymethyl-2-methylpyrimidine (HMP) moiety of thiamine is synthesized from 5-aminoimidazole ribotide (AIR), a branch point metabolite of purine and thiamine biosynthesis. ThiC is a member of the radical S-adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical rearrangement of AIR to HMP-P. As reconstituted in vitro, the ThiC reaction requires AdoMet, AIR, and reductant. This study analyzed variants of ThiC in vivo and in vitro to probe the metabolic network surrounding AIR in Salmonella enterica. Several variants of ThiC that required metabolic perturbations to function in vivo were biochemically characterized in vitro. Results presented herein indicate that the subtleties of the metabolic network have not been captured in the current reconstitution of the ThiC reaction.
PMCID: PMC3486400  PMID: 22961850
4.  Cellulosic Biomass Pretreatment and Sugar Yields as a Function of Biomass Particle Size 
PLoS ONE  2014;9(6):e100836.
Three lignocellulosic pretreatment techniques (ammonia fiber expansion, dilute acid and ionic liquid) are compared with respect to saccharification efficiency, particle size and biomass composition. In particular, the effects of switchgrass particle size (32–200) on each pretreatment regime are examined. Physical properties of untreated and pretreated samples are characterized using crystallinity, surface accessibility measurements and scanning electron microscopy (SEM) imaging. At every particle size tested, ionic liquid (IL) pretreatment results in greater cell wall disruption, reduced crystallinity, increased accessible surface area, and higher saccharification efficiencies compared with dilute acid and AFEX pretreatments. The advantages of using IL pretreatment are greatest at larger particle sizes (>75 µm).
PMCID: PMC4074075  PMID: 24971883
5.  Glycoside Hydrolases from a targeted Compost Metagenome, activity-screening and functional characterization 
BMC Biotechnology  2012;12:38.
Metagenomics approaches provide access to environmental genetic diversity for biotechnology applications, enabling the discovery of new enzymes and pathways for numerous catalytic processes. Discovery of new glycoside hydrolases with improved biocatalytic properties for the efficient conversion of lignocellulosic material to biofuels is a critical challenge in the development of economically viable routes from biomass to fuels and chemicals.
Twenty-two putative ORFs (open reading frames) were identified from a switchgrass-adapted compost community based on sequence homology to related gene families. These ORFs were expressed in E. coli and assayed for predicted activities. Seven of the ORFs were demonstrated to encode active enzymes, encompassing five classes of hemicellulases. Four enzymes were over expressed in vivo, purified to homogeneity and subjected to detailed biochemical characterization. Their pH optima ranged between 5.5 - 7.5 and they exhibit moderate thermostability up to ~60-70°C.
Seven active enzymes were identified from this set of ORFs comprising five different hemicellulose activities. These enzymes have been shown to have useful properties, such as moderate thermal stability and broad pH optima, and may serve as the starting points for future protein engineering towards the goal of developing efficient enzyme cocktails for biomass degradation under diverse process conditions.
PMCID: PMC3477009  PMID: 22759983
6.  Directed evolution: new parts and optimized function 
Current opinion in biotechnology  2009;20(4):486-491.
Constructing novel biological systems that function in a robust and predictable manner requires better methods for discovering new functional molecules and for optimizing their assembly in novel biological contexts. By enabling functional diversification and optimization in the absence of detailed mechanistic understanding, directed evolution is a powerful complement to ‘rational’ engineering approaches. Aided by clever selection schemes, directed evolution has generated new parts for genetic circuits, cell-cell communication systems, and non-natural metabolic pathways in bacteria.
PMCID: PMC2775421  PMID: 19720520
Synthetic Biology; Transcription Factors; Genetic Circuits; Evolution; Molecular; Protein Engineering; Metabolic Engineering
7.  A Mutant Allele of rpoD Results in Increased Conversion of Aminoimidazole Ribotide to Hydroxymethyl Pyrimidine in Salmonella enterica 
Journal of Bacteriology  2004;186(12):4034-4037.
An allele of rpoD (rpoD1181) that results in increased synthesis of the pyrimidine moiety of thiamine in Salmonella enterica was identified. The S508Y substitution caused by rpoD1181 is analogous to the S506F derivative of the Escherichia coli protein. The properties of this E. coli mutant protein have been well characterized in vitro. Identification of a metabolic phenotype caused by the rpoD1181 allele of S. enterica allows past in vitro results to be incorporated in continuing efforts to understand cellular processes that are integrated with the thiamine biosynthetic pathway.
PMCID: PMC419934  PMID: 15175319

Results 1-7 (7)