The Umbrella Sensor Package

In collaboration with The Morton Arboretum, the team developed an environmental sensor package for use in arboreal canopies through drone deployment. The device measures temperature, humidity, ambient light, UV, and particulate matter, recording all logged data to an onboard microSD card. The environmental sensor package can be autonomously stationed in a tree\u27s canopy for up to six months

Gene set control analysis predicts hematopoietic control mechanisms from genome-wide transcription factor binding data

Transcription factors are key regulators of both normal and malignant hematopoiesis. Chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing (ChIP-Seq) has become the method of choice to interrogate the genome-wide effect of transcription factors. We have collected and integrated 142 publicly available ChIP-Seq datasets for both normal and leukemic murine blood cell types. In addition, we introduce the new bioinformatic tool Gene Set Control Analysis (GSCA). GSCA predicts likely upstream regulators for lists of genes based on statistical significance of binding event enrichment within the gene loci of a user-supplied gene set. We show that GSCA analysis of lineage-restricted gene sets reveals expected and previously unrecognized candidate upstream regulators. Moreover, application of GSCA to leukemic gene sets allowed us to predict the reactivation of blood stem cell control mechanisms as a likely contributor to LMO2 driven leukemia. It also allowed us to clarify the recent debate on the role of Myc in leukemia stem cell transcriptional programs. As a result, GSCA provides a valuable new addition to analyzing gene sets of interest, complementary to Gene Ontology and Gene Set Enrichment analyses. To facilitate access to the wider research community, we have implemented GSCA as a freely accessible web tool (http://bioinformatics.cscr.cam.ac.uk/GSCA/GSCA.html)

Temporal spatial and metabolic measures of walking in highly functional individuals with lower limb amputations

OBJECTIVE: The aim of this descriptive exploratory study is to record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses and following completion of comprehensive rehabilitation, to able-bodied controls. DESIGN: Cross-sectional SETTING: Multi-disciplinary comprehensive rehabilitation centre PARTICIPANTS: Thirty severely injured United Kingdom military personnel with amputation and subsequent completion of their rehabilitation programme (10 unilateral trans-tibial, 10 unilateral trans-femoral, and 10 bilateral trans-femoral) were compared to (and of similar age, height and mass (p < 0.537) as) 10 able-bodied controls. INTERVENTIONS: Not applicable Main Outcomes and Measures: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at self-selected speed. RESULTS: The individuals with amputation were all male, with a mean age 29 years (SD = 4) and mean New Injury Severity Score of 31 (SD = 16). Walking speed, stride length, step length and cadence of individuals with a unilateral trans-tibial or trans-femoral amputation was comparable to controls, and only for individuals with a bilateral trans-femoral amputation was walking speed significantly slower (1·12m/s, p = 0.025) and cadence reduced (96 steps/min, p = 0.026). Oxygen cost for individuals with a unilateral trans-tibial amputation (0·15 ml/kg/m) was the same as for controls (0·15 ml/kg/m), and significantly increased by 20% (0·18ml/kg/m, p = 0.023) for unilateral trans-femoral and by 60% (0·24 ml/kg/m, p < 0.001) for bilateral trans-femoral individuals with amputation. CONCLUSION: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that the individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable to a small number of studies reporting similar outcomes for individuals with a unilateral trans-tibial amputation, but the results from this study are better than those on individuals with trans-femoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation programme. This suggests that such a programme may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve

Psychometric evaluation of the Osteoporosis Patient Treatment Satisfaction Questionnaire (OPSAT-Q™), a novel measure to assess satisfaction with bisphosphonate treatment in postmenopausal women

BACKGROUND: The Osteoporosis Patient Satisfaction Questionnaire (OPSAT-Q) is a new measure of patient satisfaction with bisphosphonate treatment for osteoporosis. The objective of this study was to evaluate the psychometric characteristics of the OPSAT-Q. METHODS: The OPSAT-Q contains 16 items in four subscales: Convenience, Confidence with Daily Activities, Side Effects, and Overall Satisfaction. All four subscale scores and an overall composite satisfaction score (CSS) can be computed. The OPSAT-Q, Osteoporosis Targeted Quality of Life (OPTQoL), and sociodemographic/clinical questionnaires, including 3 global items on convenience, functioning and side effects, were self-administered to women with osteoporosis or osteopenia recruited from four US clinics. Analyses included item and scale performance, internal consistency reliability, reproducibility, and construct validity. Reproducibility was measured using the intraclass correlation coefficient (ICC) via a follow-up questionnaire completed by participants 2 weeks post baseline. RESULTS: 104 women with a mean age of 65.1 years participated. The majority were Caucasian (64.4%), living with someone (74%), and not currently employed (58.7%). 73% had osteoporosis and 27% had osteopenia. 80% were taking weekly bisphosphonates and 18% were taking daily medication (2% missing data). On a scale of 0–100, individual patient subscale scores ranged from 17 to 100 and CSS scores ranged from 44 to 100. All scores showed acceptable internal consistency reliability (Cronbach's alpha > 0.70) (range 0.72 to 0.89). Reproducibility ranged from 0.62 (Daily Activities) to 0.79 (Side Effects) for the subscales; reproducibility for the CSS was 0.81. Significant correlations were found between the OPSAT-Q subscales and conceptually similar global measures (p < 0.001). CONCLUSION: The findings from this study confirm the validity and reliability of the OPSAT-Q and support the proposed composition of four subscales and a composite score. They also support the use of the OPSAT-Q to examine the impact of bisphosphonate dosing frequency on patient satisfaction

Randomized Noninferiority Trial of Telephone vs In-Person Genetic Counseling for Hereditary Breast and Ovarian Cancer: A 12-Month Follow-Up

Background: Telephone delivery of genetic counseling is an alternative to in-person genetic counseling because it may extend the reach of genetic counseling. Previous reports have established the noninferiority of telephone counseling on short-term psychosocial and decision-making outcomes. Here we examine the long-term impact of telephone counseling (TC) vs inperson counseling (usual care [UC]). Methods: We recruited high-risk women for a noninferiority trial comparing TC with UC. Of 1057 potentially eligible women, 669 were randomly assigned to TC (n = 335) or UC (n = 334), and 512 completed the 12-month follow-up. Primary outcomes were patient-reported satisfaction with genetic testing decision, distress, and quality of life. Secondary outcomes were uptake of cancer risk management strategies. Results: TC was noninferior to UC on all primary outcomes. Satisfaction with decision (d = 0.13, lower bound of 97.5% confidence interval [CI] = -0.34) did not cross its one-point noninferiority limit, cancer-specific distress (d = -2.10, upper bound of 97.5% CI = -0.07) did not cross its four-point noninferiority limit, and genetic testing distress (d = -0.27, upper bound of 97.5% CI = 1.46), physical function (d = 0.44, lower bound of 97.5% CI = -0.91) and mental function (d = -0.04, lower bound of 97.5% CI = -1.44) did not cross their 2.5-point noninferiority limit. Bivariate analyses showed no differences in risk-reducing mastectomy or oophorectomy across groups; however, when combined, TC had significantly more risk-reducing surgeries than UC (17.8% vs 10.5%; chi(2) = 4.43, P = .04). Conclusions: Findings support telephone delivery of genetic counseling to extend the accessibility of this service without long-termadverse outcomes.This study was supported by grants (R01 CA108933 and P30 CA051008) from the National Cancer Institute and by the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research.Peer Reviewe

The Zea mays mutants opaque-2 and opaque-7 disclose extensive changes in endosperm metabolism as revealed by protein, amino acid, and transcriptome-wide analyses

<p>Abstract</p> <p>Background</p> <p>The changes in storage reserve accumulation during maize (<it>Zea mays </it>L.) grain maturation are well established. However, the key molecular determinants controlling carbon flux to the grain and the partitioning of carbon to starch and protein are more elusive. The <it>Opaque-2 </it>(<it>O2</it>) gene, one of the best-characterized plant transcription factors, is a good example of the integration of carbohydrate, amino acid and storage protein metabolisms in maize endosperm development. Evidence also indicates that the <it>Opaque-7 </it>(<it>O7</it>) gene plays a role in affecting endosperm metabolism. The focus of this study was to assess the changes induced by the <it>o2 </it>and <it>o7 </it>mutations on maize endosperm metabolism by evaluating protein and amino acid composition and by transcriptome profiling, in order to investigate the functional interplay between these two genes in single and double mutants.</p> <p>Results</p> <p>We show that the overall amino acid composition of the mutants analyzed appeared similar. Each mutant had a high Lys and reduced Glx and Leu content with respect to wild type. Gene expression profiling, based on a unigene set composed of 7,250 ESTs, allowed us to identify a series of mutant-related down (17.1%) and up-regulated (3.2%) transcripts. Several differentially expressed ESTs homologous to genes encoding enzymes involved in amino acid synthesis, carbon metabolism (TCA cycle and glycolysis), in storage protein and starch metabolism, in gene transcription and translation processes, in signal transduction, and in protein, fatty acid, and lipid synthesis were identified. Our analyses demonstrate that the mutants investigated are pleiotropic and play a critical role in several endosperm-related metabolic processes. Pleiotropic effects were less evident in the <it>o7 </it>mutant, but severe in the <it>o2 </it>and <it>o2o7 </it>backgrounds, with large changes in gene expression patterns, affecting a broad range of kernel-expressed genes.</p> <p>Conclusion</p> <p>Although, by necessity, this paper is descriptive and more work is required to define gene functions and dissect the complex regulation of gene expression, the genes isolated and characterized to date give us an intriguing insight into the mechanisms underlying endosperm metabolism.</p

Expansion of the Human Phenotype Ontology (HPO) knowledge base and resources.

The Human Phenotype Ontology (HPO)-a standardized vocabulary of phenotypic abnormalities associated with 7000+ diseases-is used by thousands of researchers, clinicians, informaticians and electronic health record systems around the world. Its detailed descriptions of clinical abnormalities and computable disease definitions have made HPO the de facto standard for deep phenotyping in the field of rare disease. The HPO\u27s interoperability with other ontologies has enabled it to be used to improve diagnostic accuracy by incorporating model organism data. It also plays a key role in the popular Exomiser tool, which identifies potential disease-causing variants from whole-exome or whole-genome sequencing data. Since the HPO was first introduced in 2008, its users have become both more numerous and more diverse. To meet these emerging needs, the project has added new content, language translations, mappings and computational tooling, as well as integrations with external community data. The HPO continues to collaborate with clinical adopters to improve specific areas of the ontology and extend standardized disease descriptions. The newly redesigned HPO website (www.human-phenotype-ontology.org) simplifies browsing terms and exploring clinical features, diseases, and human genes

Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution.

Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists

Biomedical Discovery Acceleration, with Applications to Craniofacial Development

The profusion of high-throughput instruments and the explosion of new results in the scientific literature, particularly in molecular biomedicine, is both a blessing and a curse to the bench researcher. Even knowledgeable and experienced scientists can benefit from computational tools that help navigate this vast and rapidly evolving terrain. In this paper, we describe a novel computational approach to this challenge, a knowledge-based system that combines reading, reasoning, and reporting methods to facilitate analysis of experimental data. Reading methods extract information from external resources, either by parsing structured data or using biomedical language processing to extract information from unstructured data, and track knowledge provenance. Reasoning methods enrich the knowledge that results from reading by, for example, noting two genes that are annotated to the same ontology term or database entry. Reasoning is also used to combine all sources into a knowledge network that represents the integration of all sorts of relationships between a pair of genes, and to calculate a combined reliability score. Reporting methods combine the knowledge network with a congruent network constructed from experimental data and visualize the combined network in a tool that facilitates the knowledge-based analysis of that data. An implementation of this approach, called the Hanalyzer, is demonstrated on a large-scale gene expression array dataset relevant to craniofacial development. The use of the tool was critical in the creation of hypotheses regarding the roles of four genes never previously characterized as involved in craniofacial development; each of these hypotheses was validated by further experimental work

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups