Biases in the Experimental Annotations of Protein Function and their Effect on Our Understanding of Protein Function Space

The ongoing functional annotation of proteins relies upon the work of curators to capture experimental findings from scientific literature and apply them to protein sequence and structure data. However, with the increasing use of high-throughput experimental assays, a small number of experimental studies dominate the functional protein annotations collected in databases. Here we investigate just how prevalent is the "few articles -- many proteins" phenomenon. We examine the experimentally validated annotation of proteins provided by several groups in the GO Consortium, and show that the distribution of proteins per published study is exponential, with 0.14% of articles providing the source of annotations for 25% of the proteins in the UniProt-GOA compilation. Since each of the dominant articles describes the use of an assay that can find only one function or a small group of functions, this leads to substantial biases in what we know about the function of many proteins. Mass-spectrometry, microscopy and RNAi experiments dominate high throughput experiments. Consequently, the functional information derived from these experiments is mostly of the subcellular location of proteins, and of the participation of proteins in embryonic developmental pathways. For some organisms, the information provided by different studies overlap by a large amount. We also show that the information provided by high throughput experiments is less specific than those provided by low throughput experiments. Given the experimental techniques available, certain biases in protein function annotation due to high-throughput experiments are unavoidable. Knowing that these biases exist and understanding their characteristics and extent is important for database curators, developers of function annotation programs, and anyone who uses protein function annotation data to plan experiments.Comment: Accepted to PLoS Computational Biology. Press embargo applies. v4: text corrected for style and supplementary material inserte

Challenges and new opportunities for detecting endogenous opioid peptides in reward

The endogenous opioid peptide system, comprised of enkephalins, endorphins, dynorphins, and nociceptin, is a highly complex neurobiological system. Opioid peptides are derived from four precursor molecules and undergo several processing events yielding over 20 unique opioid peptides. This diversity together with lo

Koinonia

Spotlight FeatureThe Cult of Cool: Rejecting Relevance and Pursuing Faithfulness, Kate Bowman Johnston ReflectionFaith and the Problem of Suffering, James Spiegel ACSD Summer 2006Photos from ACSE Author InterviewOur Place at the Table: The Role of White People in Racial Reconciliation: An Interview with Doug Schaupp, Glen Kinoshita Thinking TheologicallyThinking Theologically: The Seasons of Hope\u27s Redemption Part I, Todd Ream Book ReviewSkin Games, reviewed by Jessie M. Brown FeaturesThe President\u27s Corner Editor\u27s Deskhttps://pillars.taylor.edu/acsd_koinonia/1006/thumbnail.jp

Tool Measures Depths of Defects on a Case Tang Joint

A special-purpose tool has been developed for measuring the depths of defects on an O-ring seal surface. The surface lies in a specially shaped ringlike fitting, called a capture feature tang, located on an end of a cylindrical segment of a case that contains a solid-fuel booster rocket motor for launching a space shuttle. The capture feature tang is a part of a tang-and-clevis, O-ring joint between the case segment and a similar, adjacent cylindrical case segment. When the segments are joined, the tang makes an interference fit with the clevis and squeezes the O-ring at the side of the gap

Propagation of Pi2 pulsations through the braking region in global MHD simulations

We investigate the propagation of Pi2 period pulsations from their origin in the plasma sheet through the braking region, the region where the fast flows are slowed as they approach the inner edge of the plasma sheet. Our approach is to use both the University of California, Los Angeles (UCLA) and Lyonâ Fedderâ Mobarry (LFM) global magnetohydrodynamic (MHD) computer codes to simulate the Earth’s magnetosphere during a substorm that occurred on 14 September 2004 when Pi2 pulsations were observed. We use two different MHD models in order to test the robustness of our conclusions about Pi2. The simulations are then compared with groundâ based and satellite data. We find that the propagation of the pulsations in the simulations, especially through the braking region, depends strongly on the ionospheric models used at the inner boundary of the MHD models. With respect to typical observed values, the modeled conductances are high in the UCLA model and low in the LFM model. The different conductances affect the flows, producing stronger line tying that slows the flow in the braking region more in the UCLA model than in the LFM model. Therefore, perturbations are able to propagate much more freely into the inner magnetosphere in the LFM results. However, in both models Pi2 period perturbations travel with the dipolarization front (DF) that forms at the earthward edge of the flow channel, but as the DF slows in the braking region, â 8â ¤xâ ¤â 6 RE, the Pi2 period perturbations begin to travel ahead of it into the inner magnetosphere. This indicates that the flow channels generate compressional waves with periods that fall within the Pi2 range and that, as the flows themselves are stopped in the braking region, the compressional wave continues to propagate into the inner magnetosphere.Key PointsPi2 travel with DFs until the DFs slow in the braking region and the Pi2 begin to run ahead of themIonospheric parameters strongly affect how Pi2 are able to propagateBoth the UCLA and LFM models show similar results for Pi2 propagation outside of â ¼â 7 REPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134917/1/jgra52317_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134917/2/jgra52317.pd

Studies of thermionic materials for space power applications informal monthly report, oct. 1 - oct. 31, 1963

Thermionic space power material - isostatic pressing, vapor deposited tungsten, high temperature properties, cesium thermionic cell life testing, and irradiation studie

Enhancing the experience of carers in the chemotherapy outpatient setting: an exploratory randomised controlled trial to test impact, acceptability and feasibility of a complex intervention co-designed by carers and staff

PurposeSupporting someone through chemotherapy can be emotionally and physically demanding. However, research has yet to establish the type of support carers require or the best way to provide this. This study tested the feasibility and acceptability of a complex intervention for carers that was co-designed by staff and carers of patients starting chemotherapy.MethodsForty-seven carers were recruited, randomised between the intervention (n?=?24) and control (n?=?23) groups. A questionnaire was completed pre- and post-intervention measuring knowledge of chemotherapy and its side effects, experience of care, satisfaction with outpatient services, coping and emotional wellbeing. The intervention process was evaluated by carers and healthcare professionals (HCPs) in focus groups.ResultsRecruitment to the study was unproblematic and attrition from it was low, suggesting the intervention and study processes were acceptable to patients and carers. Carers in receipt of the ‘Take Care’ intervention reported statistically significantly better understanding of symptoms and side effects and their information needs being more frequently met than carers in the control. Confidence in coping improved between baseline and follow-up for the intervention group and declined for the control although differences were insufficient to achieve statistical significance. There was no significant difference between the two groups’ emotional wellbeing. HCP and carer focus groups confirmed the feasibility and acceptability of the intervention.ConclusionsThe ‘Take Care’ intervention proved acceptable to carers and HCPs and demonstrates considerable promise and utility in practice. Study findings support the conduct of a fully powered RCT to determine the intervention’s effectiveness and cost-effectiveness

CanWalk: a feasibility study with embedded randomised controlled trial pilot of a walking intervention for people with recurrent or metastatic cancer.

Objectives: Walking is an adaptable, inexpensive and accessible form of physical activity. However its impact on quality of life and symptom severity in people with advanced cancer is unknown. This study aimed to assess the feasibility and acceptability of a randomised controlled trial (RCT) of a community-based walking intervention to enhance quality of life (QoL) in people with recurrent/metastatic cancer. Design: We used a mixed-methods design comprising a two-centre RCT and nested qualitative interviews. Participants: Patients with advanced breast, prostate, gynaecological or haematological cancers randomised 1:1 between intervention and usual care. Intervention: The intervention comprised Macmillan’s ‘Move More’ information, a short motivational interview with a recommendation to walk for at least 30 minutes on alternate days and attend a volunteer-led group walk weekly. Outcomes: we assessed feasibility and acceptability of the intervention and RCT by evaluating study processes (rates of recruitment, consent, retention, adherence and adverse events), and using end of study questionnaires and qualitative interviews. Patient reported outcome measures (PROMS) assessing quality of life (QoL), activity, fatigue, mood and self-efficacy were completed at baseline and 6, 12 and 24 weeks. Results: We recruited 42 (38%) of eligible participants. Recruitment was lower than anticipated (goal n=60), the most commonly reported reason being unable to commit to walking groups (n=19). Randomisation procedures worked well with groups evenly matched for age, sex and activity. By week 24, there was a 45% attrition rate. Most PROMs whilst acceptable were not sensitive to change and did not capture key benefits. Conclusions: The intervention was acceptable, well tolerated and the study design was judged acceptable and feasible. Results are encouraging and demonstrate that exercise was popular and conveyed benefit to participants. Consequently, an effectiveness RCT is warranted, with some modifications to the intervention to include greater tailoring and more appropriate PROMs selected.</p