18 research outputs found

    The Structure-Function Linkage Database

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    The Structure–Function Linkage Database (SFLD, http://sfld.rbvi.ucsf.edu/) is a manually curated classification resource describing structure–function relationships for functionally diverse enzyme superfamilies. Members of such superfamilies are diverse in their overall reactions yet share a common ancestor and some conserved active site features associated with conserved functional attributes such as a partial reaction. Thus, despite their different functions, members of these superfamilies ‘look alike’, making them easy to misannotate. To address this complexity and enable rational transfer of functional features to unknowns only for those members for which we have sufficient functional information, we subdivide superfamily members into subgroups using sequence information, and lastly into families, sets of enzymes known to catalyze the same reaction using the same mechanistic strategy. Browsing and searching options in the SFLD provide access to all of these levels. The SFLD offers manually curated as well as automatically classified superfamily sets, both accompanied by search and download options for all hierarchical levels. Additional information includes multiple sequence alignments, tab-separated files of functional and other attributes, and sequence similarity networks. The latter provide a new and intuitively powerful way to visualize functional trends mapped to the context of sequence similarity

    Annotation Error in Public Databases: Misannotation of Molecular Function in Enzyme Superfamilies

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    Due to the rapid release of new data from genome sequencing projects, the majority of protein sequences in public databases have not been experimentally characterized; rather, sequences are annotated using computational analysis. The level of misannotation and the types of misannotation in large public databases are currently unknown and have not been analyzed in depth. We have investigated the misannotation levels for molecular function in four public protein sequence databases (UniProtKB/Swiss-Prot, GenBank NR, UniProtKB/TrEMBL, and KEGG) for a model set of 37 enzyme families for which extensive experimental information is available. The manually curated database Swiss-Prot shows the lowest annotation error levels (close to 0% for most families); the two other protein sequence databases (GenBank NR and TrEMBL) and the protein sequences in the KEGG pathways database exhibit similar and surprisingly high levels of misannotation that average 5%–63% across the six superfamilies studied. For 10 of the 37 families examined, the level of misannotation in one or more of these databases is >80%. Examination of the NR database over time shows that misannotation has increased from 1993 to 2005. The types of misannotation that were found fall into several categories, most associated with “overprediction” of molecular function. These results suggest that misannotation in enzyme superfamilies containing multiple families that catalyze different reactions is a larger problem than has been recognized. Strategies are suggested for addressing some of the systematic problems contributing to these high levels of misannotation

    Bridging gaps in traditional research training with iBiology Courses.

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    iBiology Courses provide trainees with just-in-time learning resources to become effective researchers. These courses can help scientists build core research skills, plan their research projects and careers, and learn from scientists with diverse backgrounds

    Elements of iBiology Courses that contribute to student learning and meaningful interactions with mentors.

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    (01) The course lessons contain different modalities, such as videos and interactive prompts, designed to engage diverse learners and deepen their skills and knowledge. (02) By answering a series of reflective prompts throughout the course, participants create tangible plans that outline their goals, approaches, and anticipated outcomes relevant to the skills they want to develop in the lab. In each course, participants are directed to share their plans with mentors to receive feedback and guidance. (03) The courses include several ways for participants to personalize their own learning. (04) The most helpful learning components as identified by participants in surveys. BCLS, Business Concepts for Life Scientists; LE, Let’s Experiment; PYSJ, Planning Your Scientific Journey; SYR, Share Your Research.</p
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