The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of pathway/genome databases

The MetaCyc database (MetaCyc.org) is a comprehensive and freely accessible resource for metabolic pathways and enzymes from all domains of life. The pathways in MetaCyc are experimentally determined, small-molecule metabolic pathways and are curated from the primary scientific literature. With more than 1400 pathways, MetaCyc is the largest collection of metabolic pathways currently available. Pathways reactions are linked to one or more well-characterized enzymes, and both pathways and enzymes are annotated with reviews, evidence codes, and literature citations. BioCyc (BioCyc.org) is a collection of more than 500 organism-specific Pathway/Genome Databases (PGDBs). Each BioCyc PGDB contains the full genome and predicted metabolic network of one organism. The network, which is predicted by the Pathway Tools software using MetaCyc as a reference, consists of metabolites, enzymes, reactions and metabolic pathways. BioCyc PGDBs also contain additional features, such as predicted operons, transport systems, and pathway hole-fillers. The BioCyc Web site offers several tools for the analysis of the PGDBs, including Omics Viewers that enable visualization of omics datasets on two different genome-scale diagrams and tools for comparative analysis. The BioCyc PGDBs generated by SRI are offered for adoption by any party interested in curation of metabolic, regulatory, and genome-related information about an organism

Combining the contributions of behavioral economics and other social sciences in understanding taxation and tax reform

This paper extends previous work presented at the SABE/IAREP conference at St Mary’s University, Halifax (James, 2009). In the earlier paper it was shown that conventional economic theory is used to make the case for tax reform but does not always adequately incorporate all the relevant factors. However, an approach based on behavioral economics can make the difference between success and failure. In this paper the contributions of other social sciences are also included. Taxation is a particularly appropriate subject to explore the integration of the social sciences since they have all devoted considerable attention to it. It can be seen that different social sciences suggest a range of variables that might be taken into account in addition to those included in mainstream economics. Other social sciences also offer different methodological approaches and consider the possibility of different outcomes of the fiscal process. The paper concludes that it is not easy to integrate the social sciences in a single approach to the study of tax and tax policy. There may also be the risk of encouraging inappropriate integration - researchers operating outside their expertise can produce results that are not helpful. However, comparing the contribution of behavioral economics with those of the social sciences more generally, it can be seen that behavioral economics can offer a framework within which these areas can be examined. Indeed, it may be a useful channel to add the contributions of other social sciences to mainstream economic research

Finding Sequences for over 270 Orphan Enzymes

<div><p>Despite advances in sequencing technology, there are still significant numbers of well-characterized enzymatic activities for which there are no known associated sequences. These ‘orphan enzymes’ represent glaring holes in our biological understanding, and it is a top priority to reunite them with their coding sequences. Here we report a methodology for resolving orphan enzymes through a combination of database search and literature review. Using this method we were able to reconnect over 270 orphan enzymes with their corresponding sequence. This success points toward how we can systematically eliminate the remaining orphan enzymes and prevent the introduction of future orphan enzymes.</p></div

The end-to-end process of resolving an orphan enzyme may include literature searches, database searches, and laboratory work.

<p>Beginning with a putative orphan enzyme (POE) (yellow), an investigator can maximize the likelihood of finding sequence data while minimizing effort by following a few steps. An immediate search of the OEP database will indicate if the orphan is already recognized as such and give the researcher access to any data about that orphan enzyme that others have already collected, including if it has been resolved (and perhaps the link between sequence and activity simply haven't been propagated to major sequence databases yet). The next steps are to carry out a literature and database evaluation of the orphan and then potentially follow that with laboratory identification. It may be helpful to submit information about the orphan enzyme, including the fact that it exists as well as any supporting identification information, to the OEP web site at the two marked points in the process (OEP symbols). This makes the information available to others in the research community who may be able to help identify sequence for the enzyme activity.</p

Putative orphan enzymes were evaluated via the literature and databases to find sequences or identification information.

<p>Each putative orphan was evaluated via a multistep process relying on sequence databases, the literature, and patent databases. Each evaluation process began by collecting all names for the enzyme activity. The BRENDA and MetaCyc databases, which link enzyme data to EC numbers, were then examined. At this and all subsequent steps, sequence data was collected when found. Documents were then collected, including texts cited in BRENDA and MetaCyc, texts found via PubMed search, and patents from the U.S. Patent and Trademark Office. Identification information (inset box) were collected from each publication. When available, peptide sequence data were collected to attempt to identify the full protein sequence via BLAST. When possible, identification information were used to predict candidate sequences for subsequent testing in the laboratory.</p

Sequences were identified for 275 putative orphan enzymes, most frequently by fixing database errors.

<p>Sequences were found for 275 putative orphan enzymes (25% of the total) by searching through the literature, sequence databases, and patents. Approximately half of the orphans for which sequences could be found were “annotation updates,” in which the sequence for the enzyme in major databases was annotated with no activity, with a less specific activity, with an incorrect activity that was in the same general class as the correct one, or with another <i>correct</i> activity that the enzyme also carries out. The remaining orphans fell into the “data inconsistency” category. Orphan enzymes in this category were in some way annotated to sequence data, but a lack of an EC number or a nomenclature mismatch meant that searching these databases for the activity did not yield any sequence data.</p