Multiple Search Engines Research Articles

The prevalence of cobalamin deficiency among vegetarians assessed by serum vitamin B12: a review of literature

Individuals following vegetarian diets are at risk for developing vitamin B12 deficiency owing to suboptimal intake. As vitamin B12 is essential for the synthesis of nucleic acids, erythrocytes and in the maintenance of myelin, deficiency may result in a variety of symptoms. Some of these symptoms may be severe while others may be irreversible. The objective of this review was to assess vitamin B12 deficiency, based on reported serum vitamin B12, among individuals adhering to different types of vegetarian diets. A systematic literature search was carried out using multiple search engines including PubMed, Medline, CINAHL plus, ERIC, Nursing and Allied Health Collection and Nursing/Academic Edition. The inclusion criteria consisted of original studies that assessed serum vitamin B12, studies written in English, non-case studiesand studies that reported actual percentages of vitamin B12 deficiency. Forty research studies were included. The deficiency prevalence among infants reached 45%. The deficiency among the children and adolescents ranged from 0 to 33.3%. Deficiency among pregnant women ranged from 17 to 39%, dependent on the trimester. Adults and elderly individuals had a deficiency range of 0-86.5%. Higher deficiency prevalence was reported in vegans than in other vegetarians. Thus, with few exceptions, the reviewed studies documented relatively high deficiency prevalence among vegetarians. Vegans who do not ingest vitamin B12 supplements were found to be at especially high risk. Vegetarians, especially vegans, should give strong consideration to the use of vitamin B12 supplements to ensure adequate vitamin B12 intake. Vegetarians, regardless of the type of vegetarian diet they adhere to, should be screened for vitamin B12 deficiency.

A Profile of Acute Care in an Aging America: Snowball Sample Identification and Characterization of United States Geriatric Emergency Departments in 2013

The aging of America poses a challenge to emergency departments (EDs). Studies show that elderly patients have poor outcomes despite increased testing, prolonged periods of observation, and higher admission rates. In response, emergency medicine (EM) leaders have implemented strategies for improved ED elder care, enhancing expertise, equipment, policies, and protocols. One example is the development of geriatric EDs gaining in popularity nationwide. To the authors' knowledge, this is the first research to systematically identify and qualitatively characterize the existence, locations, and features of geriatric EDs across the United States. The primary objective was to determine the number, distribution, and characteristics of geriatric EDs in the United States in 2013. This was a survey with potential respondents identified via a snowball sampling of known geriatric EDs, EM professional organizations' geriatric interest groups, and a structured search of the Internet using multiple search engines. Sites were contacted by telephone, and those confirming geriatric EDs presence received the survey via e-mail. Category questions included date of opening, location, volumes, staffing, physical plant changes, screening tools, policies, and protocols. Categories were reported based on general interest to those seeking to understand components of a geriatric ED. Thirty-six hospitals confirmed geriatric ED existence and received surveys. Thirty (83%) responded to the survey and confirmed presence or plans for geriatric EDs: 24 (80%) had existing geriatric EDs, and six (20%) were planning to open geriatric EDs by 2014. The majority of geriatric EDs are located in the Midwest (46%) and Northeast (30%) regions of the United States. Eighty percent serve from 5,000 to 20,000 elder patients annually. Seventy percent of geriatric EDs are attached to the main ED, and 66% have from one to 10 geriatric beds. Physical plant changes include modifications to beds (96%), lighting (90%), flooring (83%), visual aids (73%), and sound level (70%). Seventy-seven percent have staff overlapping with the nongeriatric portion of their ED, and 80% require geriatric staff didactics. Sixty-seven percent of geriatric EDs report discharge planning for geriatric ED patients, and 90% of geriatric EDs had direct follow-up through patient callbacks. The snowball sample identification of U.S. geriatric EDs resulted in 30 confirmed respondents. There is significant variation in the components constituting a geriatric ED. The United States should consider external validation of self-identified geriatric EDs to standardize the quality and type of care patients can expect from an institution with an identified geriatric ED.

Design and implementation of Metta, a metasearch engine for biomedical literature retrieval intended for systematic reviewers.

BackgroundIndividuals and groups who write systematic reviews and meta-analyses in evidence-based medicine regularly carry out literature searches across multiple search engines linked to different bibliographic databases, and thus have an urgent need for a suitable metasearch engine to save time spent on repeated searches and to remove duplicate publications from initial consideration. Unlike general users who generally carry out searches to find a few highly relevant (or highly recent) articles, systematic reviewers seek to obtain a comprehensive set of articles on a given topic, satisfying specific criteria. This creates special requirements and challenges for metasearch engine design and implementation.MethodsWe created a federated search tool that is connected to five databases: PubMed, EMBASE, CINAHL, PsycINFO, and the Cochrane Central Register of Controlled Trials. Retrieved bibliographic records were shown online; optionally, results could be de-duplicated and exported in both BibTex and XML format.ResultsThe query interface was extensively modified in response to feedback from users within our team. Besides a general search track and one focused on human-related articles, we also added search tracks optimized to identify case reports and systematic reviews. Although users could modify preset search options, they were rarely if ever altered in practice. Up to several thousand retrieved records could be exported within a few minutes. De-duplication of records returned from multiple databases was carried out in a prioritized fashion that favored retaining citations returned from PubMed.ConclusionsSystematic reviewers are used to formulating complex queries using strategies and search tags that are specific for individual databases. Metta offers a different approach that may save substantial time but which requires modification of current search strategies and better indexing of randomized controlled trial articles. We envision Metta as one piece of a multi-tool pipeline that will assist systematic reviewers in retrieving, filtering and assessing publications. As such, Metta may find wide utility for anyone who is carrying out a comprehensive search of the biomedical literature.Electronic supplementary materialThe online version of this article (doi:10.1186/2047-2501-2-1) contains supplementary material, which is available to authorized users.

P-006 YI Treatment of Severe Ulcerative Colitis with Cyclosporine Less than 30 Days Post Acute Myocardial Infarction and Heart Failure

When intravenous (IV) steroids fail, severe ulcerative colitis (UC) is treated with cyclosporine, infliximab, or surgery. Currently, advanced heart failure is an absolute contraindication for tumor necrosis factor-alpha antagonists because of the risk of increased mortality and worsening heart failure (1,2). Cyclosporine may decrease myocardial reperfusion injury and improve left ventricular remodeling (3–8). We present a case of a patient with acute myocardial infarction (MI) and heart failure whose severe colitis was treated successfully with cyclosporine. A literature search was performed using multiple search engines (PubMed, EMBASE, CINAHL) for cases with ulcerative colitis and myocardial infarction as well as ulcerative colitis, myocardial infarction, and heart failure. A 58 year-old Haitian male with a past medical history of coronary artery disease with stents in 2001 and 2011 and history of UC, maintained on topical therapy for left-sided colitis, had a non-ST elevated myocardial infarction (NSTEMI) requiring a drug-eluting stent. Shortly after, he noticed rectal bleeding and self stopped both aspirin and clopidogrel. Two weeks later, he had a STEMI with 100% occlusion and stent re-stenosis; angioplasty and thrombectomy were performed emergently. Post-procedure echocardiogram showed ejection fraction of 30% and severely reduced left ventricular contractility. He continued to have bloody diarrhea and was found to have elevated inflammatory markers (erythrocyte sediment rate (ESR) 71, C-reactive protein (CRP) 129.4). The patient failed a trial of 5-aminosalicylates. A flexible sigmoidoscopy was consistent with severe UC. He was started on IV steroids, metronidazole, and hydrocortisone foam; 1 week later, symptoms persisted and his hemoglobin dropped to 6.2. A computed tomography scan showed pancolitis. Additionally, there was a concern for sepsis as his white blood cell count (WBC) dropped below 1,000 necessitating filgrastim. Due to his heart failure, infliximab was not an option. The mortality risk associated with colectomy was assessed to be >50% given his recent MI. He was therefore started on IV cyclosporine 2 mg/kg for 7 days; a lower dose of cyclosporine was used because of the patient’s low total cholesterol (102) and atorvastatin was held. Within 1 week, bowel movements were reduced to 3 per day, with less cramping, urgency, and tenesmus; inflammatory markers also improved (ESR 29, CRP 3.5). He was discharged on oral cyclosporine with a bridge to azathioprine. He is now 3 months post treatment and doing well. Repeat echocardiogram showed stable heart function and his WBC rose to normal and remained stable. Previous cases of UC and MI (9–14, Table 1) illustrate the various presentations, therapeutic options, and outcomes of similar patients. The only other case found in the literature of UC flare with STEMI and heart failure that was treated with cyclosporine required an emergent colectomy 2 weeks later (10). Options for treating severe UC in patients who are acutely post MI and with heart failure are limited. In this case, cyclosporine appeared to be a safer option than tumor necrosis factor-alpha antagonists.

Tools (Viewer, Library and Validator) that Facilitate Use of the Peptide and Protein Identification Standard Format, Termed mzIdentML

The Proteomics Standards Initiative has recently released the mzIdentML data standard for representing peptide and protein identification results, for example, created by a search engine. When a new standard format is produced, it is important that software tools are available that make it straightforward for laboratory scientists to use it routinely and for bioinformaticians to embed support in their own tools. Here we report the release of several open-source Java-based software packages based on mzIdentML: ProteoIDViewer, mzidLibrary, and mzidValidator. The ProteoIDViewer is a desktop application allowing users to visualize mzIdentML-formatted results originating from any appropriate identification software; it supports visualization of all the features of the mzIdentML format. The mzidLibrary is a software library containing routines for importing data from external search engines, post-processing identification data (such as false discovery rate calculations), combining results from multiple search engines, performing protein inference, setting identification thresholds, and exporting results from mzIdentML to plain text files. The mzidValidator is able to process files and report warnings or errors if files are not correctly formatted or contain some semantic error. We anticipate that these developments will simplify adoption of the new standard in proteomics laboratories and the integration of mzIdentML into other software tools. All three tools are freely available in the public domain.

Practical and Efficient Searching in Proteomics: A Cross Engine Comparison.

Analysis of large datasets produced by mass spectrometry-based proteomics relies on database search algorithms to sequence peptides and identify proteins. Several such scoring methods are available, each based on different statistical foundations and thereby not producing identical results. Here, the aim is to compare peptide and protein identifications using multiple search engines and examine the additional proteins gained by increasing the number of technical replicate analyses. A HeLa whole cell lysate was analyzed on an Orbitrap mass spectrometer for 10 technical replicates. The data were combined and searched using Mascot, SEQUEST, and Andromeda. Comparisons were made of peptide and protein identifications among the search engines. In addition, searches using each engine were performed with incrementing number of technical replicates. The number and identity of peptides and proteins differed across search engines. For all three search engines, the differences in proteins identifications were greater than the differences in peptide identifications indicating that the major source of the disparity may be at the protein inference grouping level. The data also revealed that analysis of 2 technical replicates can increase protein identifications by up to 10-15%, while a third replicate results in an additional 4-5%. The data emphasize two practical methods of increasing the robustness of mass spectrometry data analysis. The data show that 1) using multiple search engines can expand the number of identified proteins (union) and validate protein identifications (intersection), and 2) analysis of 2 or 3 technical replicates can substantially expand protein identifications. Moreover, information can be extracted from a dataset by performing database searching with different engines and performing technical repeats, which requires no additional sample preparation and effectively utilizes research time and effort.

The Impact of Methodology and Confounding Variables on the Association Between Major Depression and Coronary Heart Disease: Review and Recommendations

Background: A reciprocal association exists between Major Depressive Disorder (MDD) and Coronary Heart Disease (CHD). A quantitative evaluation of this association is necessary to identify potential areas of clinical intervention. However, the association is unclear because of methodological differences and confounders across studies. This review examines the impact of methodology and confounding variables on the magnitude of the relationship between MDD and CHD. Methods: The search terms “major depression AND coronary heart disease” were entered into an electronic multiple database search engine. Abstracts were screened for relevance and individually selected articles were collated. Results: Nine methodological issues and three confounders are identified, which have contributed to uncertainty in the quantitative relationship between MDD and CHD. More quantitative, prospective longitudinal studies are needed, which use standard definitions for MDD and CHD and define clear outcomes. Studies should clearly establish the temporal relationship between the onset of depressed mood and one or more adverse cardiac events, should use quantitative measures of depression which are treated as continuous data, and have frequent measures of mental state over time, correlated with measures of cardiac health. Study design should avoid confounding by considering demographic factors, cardiac risk factors and management of MDD in CHD patients. Conclusions: This review raises the need for a standardised methodology in future research, taking into account the biases and confounders listed. Adopting a consensus approach to methodology will facilitate the quantitative exploration of the causal network linking MDD and CHD.

Methemoglobinemia in Bronchoscopy

Methemoglobinemia results from oxidation of ferrous iron to ferric iron within the hemoglobin molecule. This molecule cannot bind oxygen and increases the affinity of normal hemoglobin for oxygen, which results in decreased oxygen offloading in peripheral tissues. At elevated levels, methemoglobinemia can cause dyspnea, cyanosis, and even death. Common local anesthesia agents have been correlated with methemoglobinemia. Bronchoscopy is a commonly performed clinical procedure which uses topical application of these anesthetics to provide patient comfort. Methylene blue is an agent thought to help reverse the effects of methemoglobinemia by facilitating the methemoglobin reductase system. Using multiple search engines including PubMed and the Cochrane Database, available data on cases of methemoglobinemia after bronchoscopy were pooled. Adult and pediatric cases were considered. Eleven cases were identified. Cases occurred from 1977 until present. Data gathering was complicated by the fact that a consistent reporting system was not used across cases. Arterial blood gas data and CO-oximetry reported levels of methemoglobin were reported where available. No patients died from methemoglobinemia. The most common finding across all patients was decreased peripheral oxygen saturation. Cyanosis was also frequently reported. There was a disparity between the low peripheral oxygen saturation which was reported and the pO(2) on the arterial blood gas. Dose and type of anesthetic agent varied widely across studies. Using topical anesthetic during bronchoscopy appears relatively safe. No fatalities from methemoglobinemia after bronchoscopy have been reported. A high suspicion for methemoglobinemia is required in patients who develop hypoxia or cyanosis postprocedurally. Access to CO-oximetry can confirm the diagnosis but the clinical picture is often sufficient to proceed with methylene blue treatment or observation, based on how severely the patient is affected. Patients who return to baseline can be considered for discharge home.

Analysis of Post‐translational Modifications

Analysis of Post‐translational Modifications

D‐score: A search engine independent MD‐score

While peptides carrying PTMs are routinely identified in gel-free MS, the localization of the PTMs onto the peptide sequences remains challenging. Search engine scores of secondary peptide matches have been used in different approaches in order to infer the quality of site inference, by penalizing the localization whenever the search engine similarly scored two candidate peptides with different site assignments. In the present work, we show how the estimation of posterior error probabilities for peptide candidates allows the estimation of a PTM score called the D-score, for multiple search engine studies. We demonstrate the applicability of this score to three popular search engines: Mascot, OMSSA, and X!Tandem, and evaluate its performance using an already published high resolution data set of synthetic phosphopeptides. For those peptides with phosphorylation site inference uncertainty, the number of spectrum matches with correctly localized phosphorylation increased by up to 25.7% when compared to using Mascot alone, although the actual increase depended on the fragmentation method used. Since this method relies only on search engine scores, it can be readily applied to the scoring of the localization of virtually any modification at no additional experimental or in silico cost.

Effective Approaches to Motivate and Engage Reluctant Boys in Literacy

AbstractThe purpose of this article was to investigate the reasons why elementary‐aged boys often lack motivation in literacy and to provide teachers with useful approaches to engage reluctant boys in reading and writing. Following a comprehensive search of multiple university data base search engines, the author critically evaluated 21 peer‐reviewed sources written within the last ten years, as well as two sources from the last 14 years. Gender‐based brain research studies revealed to the author that differences in brain design and development create learning differences between males and females. Evidence from Qualitative and Mixed Method studies also led the author to find lack of confidence, interest level, and topic choice to be significant factors affecting a boy's motivation to read and/or write. Included in the article are strategy suggestions that teachers may implement in their classrooms to better engage boys in literacy.

Rehabilitation After Anterior Cruciate Ligament Reconstruction

Rigorous rehabilitation after anterior cruciate ligament (ACL) reconstruction is necessary for a successful surgical outcome. A large number of clinical trials continue to assess aspects of this rehabilitation process. Prior systematic reviews evaluated fifty-four Level-I and II clinical trials published through 2005. Eighty-five articles from 2006 to 2010 were identified utilizing multiple search engines. Twenty-nine Level-I or II studies met inclusion criteria and were evaluated with use of the CONSORT (Consolidated Standards of Reporting Trials) criteria. Topics included in this review are postoperative bracing, accelerated strengthening, home-based rehabilitation, proprioception and neuromuscular training, and six miscellaneous topics investigated in single trials. Bracing following ACL reconstruction remains neither necessary nor beneficial and adds to the cost of the procedure. Early return to sports needs further research. Home-based rehabilitation can be successful. Although neuromuscular interventions are not likely to be harmful to patients, they are also not likely to yield large improvements in outcomes or help patients return to sports faster. Thus, they should not be performed to the exclusion of strengthening and range-of-motion exercises. Vibration training may lead to faster and more complete proprioceptive recovery but further evidence is needed. Several new modalities for rehabilitation after ACL reconstruction may be helpful but should not be performed to the exclusion of range-of-motion, strengthening, and functional exercises. Accelerated rehabilitation does not appear to be harmful but further investigation of rehabilitation timing is warranted. Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Metasearch information fusion using linear programming

For a specific query merging the returned results from multiple search engines, in the form of a metasearch aggregation, can provide significant improvement in the quality of relevant documents. This paper suggests a minimax linear programming (LP) formulation for fusion of multiple search engines results. The paper proposes a weighting method to include the importance weights of the underlying search engines. This is a two-phase approach which in the first phase a new method for computing the importance weights of the search engines is introduced and in the second stage a minimax LP model for finding relevant search engines results is formulated. To evaluate the retrieval effectiveness of the suggested method, the 50 queries of the 2002 TREC Web track were utilized and submitted to three popular Web search engines called Ask, Bing and Google. The returned results were aggregated using two exiting approaches, three high-performance commercial Web metasearch engines and our proposed technique. The efficiency of the generated lists was measured using TREC-Style Average Precision (TSAP). The new findings demonstrate that the suggested model improved the quality of merging considerably

Is Point-of-Care Ultrasound Accurate and Useful in the Hands of Military Medical Technicians? A Review of the Literature

Over the past decade, point-of-care ultrasound (US) use by nonphysician providers has grown substantially. The purpose of this article is to (1) summarize the literature evaluating military medics' facility at US, (2) more clearly define the potential utility of military prehospital US technology, and (3) lay a pathway for future research of military prehospital US. The authors performed a keyword search using multiple search engines. Each author independently reviewed the search results and evaluated the literature for inclusion. Of 30 studies identified, five studies met inclusion criteria. The applications included evaluation of cardiac activity, pneumothorax evaluation, and fracture evaluation. Additionally, a descriptive study demonstrated distribution of US exam types during practical use by Army Special Forces Medical Sergeants. No studies evaluated retention of skills over prolonged periods. Multiple studies demonstrate the feasibility of training military medics in US. Even under austere conditions, the majority of studies conclude that medic can perform US with a high degree of accuracy. Lessons learned from these studies tend to support continued use of US in out-of-hospital settings and exploration of the optimal curriculum to introduce this skill.

An overview of the Herbs in a Siddha Polyherbal decoction-Pidangunaari Kudineer indicated for Hepatomegaly

Handa et al., 1986 noted that in India, more than 87 plants are used in 33 patented and proprietary multi-ingredient plant formulations for liver protection. Siddha Materia Medica illustrates a safer, cheap and potential hepatoprotective polyherbal decoction ‘Pidangunaari kudineer’ comprised of three herbal ingredients such as leaves of Premna tomentosa, pericarp of ripe fruits of Terminalia chebula, rhizomes of Curcuma longa. This formulation is very effective against hepatitis in the clinical practice. The goal of this systematic review of the literature was to summarize the literature on the safety and hepatoprotective activity of above herbs. A manual search of bibliographies of papers identified through an Internet search using multiple search engines. Textbooks on herbal medicine and their bibliographies were also searched. Result and Conclusion: A large number of in vitro, in vivo, human clinical studies on those herbs were identified. These included studies on the antioxidant, anti-inflammatory, antihepatoxicity induced by acetaminophen and antituberculosis drugs, anticarcinogenicity, antimicrobial properties and also phytocompounds were identified to justify the safety and hepatoprotective efficacy. Ethnic background of these herbs results liver protection make Pidangunaari Kudineer for further screening for hepatoprotection.

Triage of Mechanical Ventilation for Pediatric Patients During a Pandemic

The novel H1N1 influenza pandemic renewed the concern that during a severe pandemic illness, critical care and mechanical ventilation resources will be inadequate to meet the needs of patients. Several published protocols address the need to triage patients for access to ventilator resources. However, to our knowledge, none of these has addressed the pediatric populations. We used a systematic review of the pediatric critical care literature to evaluate pediatric critical care prognosis and multisystem organ failure scoring systems. We used multiple search engines, including MEDLINE and EMBASE, using a search for terms and key words including including multiple organ failure, multiple organ dysfunction, PELOD, PRISM III, pediatric risk of mortality score, pediatric logistic organ dysfunction, pediatric index of mortality pediatric multiple organ dysfunction score, "child+multiple organ failure + scoring system." Searches were conducted in the period January 2010-February 2010. Of the 69 papers reviewed, 22 were used. Five independently derived scoring systems were evaluated for use in a respiratory pandemic ventilator triage protocol. The Pediatric Logistic Organ Dysfunction (PELOD) scoring system was the most appropriate for use in such a triage protocol. We present a pediatric-specific ventilator triage protocol using the PELOD scoring system to complement the NY State adult triage protocol. Further evaluation of pediatric scoring systems is imperative to ensure appropriate triage of pediatric patients.

Refining comparative proteomics by spectral counting to account for shared peptides and multiple search engines

Spectral counting has become a widely used approach for measuring and comparing protein abundance in label-free shotgun proteomics. However, when analyzing complex samples, the ambiguity of matching between peptides and proteins greatly affects the assessment of peptide and protein inventories, differentiation, and quantification. Meanwhile, the configuration of database searching algorithms that assign peptides to MS/MS spectra may produce different results in comparative proteomic analysis. Here, we present three strategies to improve comparative proteomics through spectral counting. We show that comparing spectral counts for peptide groups rather than for protein groups forestalls problems introduced by shared peptides. We demonstrate the advantage and flexibility of this new method in two datasets. We present four models to combine four popular search engines that lead to significant gains in spectral counting differentiation. Among these models, we demonstrate a powerful vote counting model that scales well for multiple search engines. We also show that semi-tryptic searching outperforms tryptic searching for comparative proteomics. Overall, these techniques considerably improve protein differentiation on the basis of spectral count tables.

Mind and heart: Heart rate variability in major depressive disorder and coronary heart disease - a review and recommendations

There is a reciprocal association between major depressive disorder (MDD) and coronary heart disease (CHD). These conditions are linked by a causal network of mechanisms. This causal network should be quantitatively studied and it is hypothesised that the investigation of vagal function represents a promising starting point. Heart rate variability (HRV) has been used to investigate cardiac vagal control in the context of MDD and CHD. This review aims to examine the relationship of HRV to both MDD and CHD in the context of vagal function and to make recommendations for clinical practice and research. The search terms 'heart rate variability', 'depression' and 'heart disease' were entered into an electronic multiple database search engine. Abstracts were screened for their relevance and articles were individually selected and collated. Decreased HRV is found in both MDD and CHD. Both diseases are theorized to disrupt autonomic control feedback loops on the heart and are linked to vagal function. Existing theories link vagal function to both mood and emotion as well as cardiac function. However, several factors can potentially confound HRV measures and would thus impact on a complete understanding of vagal mechanisms in the link between MDD and CHD. The quantitative investigation of vagal function using HRV represents a reasonable starting point in the study of the relationship between MDD and CHD. Many psychotropic and cardiac medications have effects on HRV, which may have clinical importance. Future studies of HRV in MDD and CHD should consider antidepressant medication, as well as anxiety, as potential confounders.

Twenty Questions for Neuroscience Metadata

Finding relevant data in the biomedical literature can be difficult sometime. To select a few neuroscience examples, suppose you would like to know (a) which serotonin receptor subunits are expressed in dentate gyrus mossy cells; (b) the average volume of the amygdala in adult male chimpanzees; (c) whether there is an EEG signature of CreutzfeldJacob disease; or (d) studies reporting bilateral fMRI activity in Brodmann area 38. These are fairly simple questions, for which standard search engines should fare relatively well. Yet even for these kinds of questions, securing the relevant information takes much longer than googling up the local weather forecast for the week-end or tomorrow’s commuter train schedule. The actual data required to build biologically realistic computational models are often more detailed: what is the time constant of the excitatory synaptic current from a specified pair of neuron types? Finding the answer in this case might require many hours or even days of queries over multiple search engines. Most importantly, the results of these queries must be typically followed by at least cursory reading of dozens of papers. When the graduate student triumphantly brings to the lab the needed reference, the adviser could mumble without lifting the eyes from the keyboard “that’s in young animals, and it was recorded at room temperature”. Another unfortunate major limitation is that, until and unless a definitive answer is found, it is usually impossible to know whether the information is available or not. In other words, existing biomedical search engines are ill-equipped to inform users that something is not yet known. Standard search algorithms such as PubMed are less than ideal to deal with data identification, because they are ultimately based on matching strings or concepts that appear in the title, abstract, and the keywords. These texts, however, are written with narrow scientific agendas in mind. The authors cannot possibly provide a list of keywords that would encompass all research projects for which some data in their articles might be relevant. If the topic of a report is the molecular phenotyping of a new genetic model of schizophrenia, the technical details of the deconvolution algorithm to deblur the optical micrographs would be nearly impossible to pick up through keyword searches. Could we devise a procedure to interrogate the scientific literature so as to extract accurately and efficiently most if not all of the relevant data? Is there a literature mining protocol that could give us the confidence that, if the query returns a blank, it means that the sought data is not yet available? Although common to all of biomedical science, this issue is particularly critical in neuroscience because of its unmatched diversity of dimensions, scales, questions, approaches, and techniques. Thus, effective tagging of publications with relevant metadata remains an outstanding neuroinformatics challenge. Full text searches provide half of the solution, in that they eliminate many of the issues related to false negatives. Many of the helpful terms to identify relevant data, for example, appear in the Materials and Methods sections of published articles rather than in their titles, abstracts, and keywords. Search engines scanning through the entire main text of publications include early visionary projects such as Textpresso, which started within the limited domain of C. elegans, then expanded to a

ModLS: Post-Translational Modification Localization Scoring with Automatic Specificity Expansion

Probability-based localisation scoring of fragment mass-spectrum phosphorylation site identifications has become common practice to confirm search engine modification assignments, and indicate the degree of certainty with which they are defined. Localisation of modifications other than phosphorylation is also required but is less commonly supported by current tools. These other modifications, such as hydroxylation, may have broad aminoacid specificity, and can be misassigned when the correct specificity is not considered in an MS database search. In addition, localisation software is often specific to a particular MS/MS search engine, and cannot be used to localise modifications identified by multiple search engines. ModLS, a new tool within our freely-available Central Proteomics Facilities Pipeline (CPFP), applies a localisation scoring method to arbitrary post-translational modifications (PTMs). As well as localising PTMs based on amino-acid specificities are included in the initial search, ModLS can automatically consider additional specificities from UniMod. This can help avoid ‘correct modification, incorrect amino-acid’ errors which can occur when data is searched using only a subset of PTM specificities. Localisation scoring can be performed on the results from any search engine incorporated within the pipeline, or where the output of individual search engines is combined to give increased coverage. We demonstrate the performance of ModLS using a publicly available phosphorylated peptide dataset, showing that it outperforms the recently characterised Mascot Delta Score approach for CID and MSA data, and is comparable for HCD data. In addition, we show the utility of automatic specificity expansion using hydroxylated and methylated peptide data. ModLS is a user-friendly localisation tool for arbitrary modifications. Its inclusion within CPFP allows PTM localisation to be performed quickly and easily on large or small result sets, from multiple search engines. Specificity expansion, introduced in ModLS, allows misassignments of modifications due to incomplete consideration of specificities to be identified and minimised.