The online Tabloid Proteome: an annotated database of protein associations.

A complete knowledge of the proteome can only be attained by determining the associations between proteins, along with the nature of these associations (e.g. physical contact in protein-protein interactions, participation in complex formation or different roles in the same pathway). Despite extensive efforts in elucidating direct protein interactions, our knowledge on the complete spectrum of protein associations remains limited. We therefore developed a new approach that detects protein associations from identifications obtained after re-processing of large-scale, public mass spectrometry-based proteomics data. Our approach infers protein association based on the co-occurrence of proteins across many different proteomics experiments, and provides information that is almost completely complementary to traditional direct protein interaction studies. We here present a web interface to query and explore the associations derived from this method, called the online Tabloid Proteome. The online Tabloid Proteome also integrates biological knowledge from several existing resources to annotate our derived protein associations. The online Tabloid Proteome is freely available through a user-friendly web interface, which provides intuitive navigation and data exploration options for the user at http://iomics.ugent.be/tabloidproteome.

MAPPI-DAT: data management and analysis for protein-protein interaction data from the high-throughput MAPPIT cell microarray platform.

Summary: Protein-protein interaction (PPI) studies have dramatically expanded our knowledge about cellular behaviour and development in different conditions. A multitude of high-throughput PPI techniques have been developed to achieve proteome-scale coverage for PPI studies, including the microarray based Mammalian Protein-Protein Interaction Trap (MAPPIT) system. Because such high-throughput techniques typically report thousands of interactions, managing and analysing the large amounts of acquired data is a challenge. We have therefore built the MAPPIT cell microArray Protein Protein Interaction-Data management & Analysis Tool (MAPPI-DAT) as an automated data management and analysis tool for MAPPIT cell microarray experiments. MAPPI-DAT stores the experimental data and metadata in a systematic and structured way, automates data analysis and interpretation, and enables the meta-analysis of MAPPIT cell microarray data across all stored experiments. Availability and Implementation: MAPPI-DAT is developed in Python, using R for data analysis and MySQL as data management system. MAPPI-DAT is cross-platform and can be ran on Microsoft Windows, Linux and OS X/macOS. The source code and a Microsoft Windows executable are freely available under the permissive Apache2 open source license at https://github.com/compomics/MAPPI-DAT. Contact: jan.tavernier@vib-ugent.be or lennart.martens@vib-ugent.be. Supplementary information: Supplementary data are available at Bioinformatics online.

Proteome-scale Binary Interactomics in Human Cells.

Because proteins are the main mediators of most cellular processes they are also prime therapeutic targets. Identifying physical links among proteins and between drugs and their protein targets is essential in order to understand the mechanisms through which both proteins themselves and the molecules they are targeted with act. Thus, there is a strong need for sensitive methods that enable mapping out these biomolecular interactions. Here we present a robust and sensitive approach to screen proteome-scale collections of proteins for binding to proteins or small molecules using the well validated MAPPIT (Mammalian Protein-Protein Interaction Trap) and MASPIT (Mammalian Small Molecule-Protein Interaction Trap) assays. Using high-density reverse transfected cell microarrays, a close to proteome-wide collection of human ORF clones can be screened for interactors at high throughput. The versatility of the platform is demonstrated through several examples. With MAPPIT, we screened a 15k ORF library for binding partners of RNF41, an E3 ubiquitin protein ligase implicated in receptor sorting, identifying known and novel interacting proteins. The potential related to the fact that MAPPIT operates in living human cells is illustrated in a screen where the protein collection is scanned for interactions with the glucocorticoid receptor (GR) in its unliganded versus dexamethasone-induced activated state. Several proteins were identified the interaction of which is modulated upon ligand binding to the GR, including a number of previously reported GR interactors. Finally, the screening technology also enables detecting small molecule target proteins, which in many drug discovery programs represents an important hurdle. We show the efficiency of MASPIT-based target profiling through screening with tamoxifen, a first-line breast cancer drug, and reversine, an investigational drug with interesting dedifferentiation and antitumor activity. In both cases, cell microarray screens yielded known and new potential drug targets highlighting the utility of the technology beyond fundamental biology.

Unbiased Protein Association Study on the Public Human Proteome Reveals Biological Connections between Co-Occurring Protein Pairs.

Mass-spectrometry-based, high-throughput proteomics experiments produce large amounts of data. While typically acquired to answer specific biological questions, these data can also be reused in orthogonal ways to reveal new biological knowledge. We here present a novel method for such orthogonal data reuse of public proteomics data. Our method elucidates biological relationships between proteins based on the co-occurrence of these proteins across human experiments in the PRIDE database. The majority of the significantly co-occurring protein pairs that were detected by our method have been successfully mapped to existing biological knowledge. The validity of our novel method is substantiated by the extremely few pairs that can be mapped to existing knowledge based on random associations between the same set of proteins. Moreover, using literature searches and the STRING database, we were able to derive meaningful biological associations for unannotated protein pairs that were detected using our method, further illustrating that as-yet unknown associations present highly interesting targets for follow-up analysis.

A Pipeline for Differential Proteomics in Unsequenced Species.

Shotgun proteomics experiments often take the form of a differential analysis, where two or more samples are compared against each other. The objective is to identify proteins that are either unique to a specific sample or a set of samples (qualitative differential proteomics), or that are significantly differentially expressed in one or more samples (quantitative differential proteomics). However, the success depends on the availability of a reliable protein sequence database for each sample. To perform such an analysis in the absence of a database, we here propose a novel, generic pipeline comprising an adapted spectral similarity score derived from database search algorithms that compares samples at the spectrum level to detect unique spectra. We applied our pipeline to compare two parasitic tapeworms: Taenia solium and Taenia hydatigena, of which only the former poses a threat to humans. Furthermore, because the genome of T. solium recently became available, we were able to prove the effectiveness and reliability of our pipeline a posteriori.

Radiotolerance of N-cycle bacteria and their transcriptomic response to low-dose space-analogue ionizing irradiation.

The advancement of regenerative life support systems (RLSS) is crucial to allow long-distance space travel. Within the Micro-Ecological Life Support System Alternative (MELiSSA), efficient nitrogen recovery from urine and other waste streams is vital to produce liquid fertilizer to feed food and oxygen production in subsequent photoautotrophic processes. This study explores the effects of ionizing radiation on nitrogen cycle bacteria that transform urea to nitrate. In particular, we assess the radiotolerance of Comamonas testosteroni, Nitrosomonas europaea, and Nitrobacter winogradskyi after exposure to acute γ-irradiation. Moreover, a comprehensive whole transcriptome analysis elucidates the effects of spaceflight-analogue low-dose ionizing radiation on the individual axenic strains and on their synthetic community o. This research sheds light on how the spaceflight environment could affect ureolysis and nitrification processes from a transcriptomic perspective.

Whole transcriptome analysis highlights nutrient limitation of nitrogen cycle bacteria in simulated microgravity.

Regenerative life support systems (RLSS) will play a vital role in achieving self-sufficiency during long-distance space travel. Urine conversion into a liquid nitrate-based fertilizer is a key process in most RLSS. This study describes the effects of simulated microgravity (SMG) on Comamonas testosteroni, Nitrosomonas europaea, Nitrobacter winogradskyi and a tripartite culture of the three, in the context of nitrogen recovery for the Micro-Ecological Life Support System Alternative (MELiSSA). Rotary cell culture systems (RCCS) and random positioning machines (RPM) were used as SMG analogues. The transcriptional responses of the cultures were elucidated. For CO2-producing C. testosteroni and the tripartite culture, a PermaLifeTM PL-70 cell culture bag mounted on an in-house 3D-printed holder was applied to eliminate air bubble formation during SMG cultivation. Gene expression changes indicated that the fluid dynamics in SMG caused nutrient and O2 limitation. Genes involved in urea hydrolysis and nitrification were minimally affected, while denitrification-related gene expression was increased. The findings highlight potential challenges for nitrogen recovery in space.

Evaluation of an English language phoneme-based imagined speech brain computer interface with low-cost electroencephalography.

Introduction: Paralyzed and physically impaired patients face communication difficulties, even when they are mentally coherent and aware. Electroencephalographic (EEG) brain-computer interfaces (BCIs) offer a potential communication method for these people without invasive surgery or physical device controls. Methods: Although virtual keyboard protocols are well documented in EEG BCI paradigms, these implementations are visually taxing and fatiguing. All English words combine 44 unique phonemes, each corresponding to a unique EEG pattern. In this study, a complete phoneme-based imagined speech EEG BCI was developed and tested on 16 subjects. Results: Using open-source hardware and software, machine learning models, such as k-nearest neighbor (KNN), reliably achieved a mean accuracy of 97 ± 0.001%, a mean F1 of 0.55 ± 0.01, and a mean AUC-ROC of 0.68 ± 0.002 in a modified one-versus-rest configuration, resulting in an information transfer rate of 304.15 bits per minute. In line with prior literature, the distinguishing feature between phonemes was the gamma power on channels F3 and F7. Discussion: However, adjustments to feature selection, trial window length, and classifier algorithms may improve performance. In summary, these are iterative changes to a viable method directly deployable in current, commercially available systems and software. The development of an intuitive phoneme-based EEG BCI with open-source hardware and software demonstrates the potential ease with which the technology could be deployed in real-world applications.

Global Soil Hydraulic Properties dataset based on legacy site observations and robust parameterization.

The representation of land surface processes in hydrological and climatic models critically depends on the soil water characteristics curve (SWCC) that defines the plant availability and water storage in the vadose zone. Despite the availability of SWCC datasets in the literature, significant efforts are required to harmonize reported data before SWCC parameters can be determined and implemented in modeling applications. In this work, a total of 15,259 SWCCs from 2,702 sites were assembled from published literature, harmonized, and quality-checked. The assembled SWCC data provide a global soil hydraulic properties (GSHP) database. Parameters of the van Genuchten (vG) SWCC model were estimated from the data using the R package 'soilhypfit'. In many cases, information on the wet- or dry-end of the SWCC measurements were missing, and we used pedotransfer functions (PTFs) to estimate saturated and residual water contents. The new database quantifies the differences of SWCCs across climatic regions and can be used to create global maps of soil hydraulic properties.

Cov-MS: A Community-Based Template Assay for Mass-Spectrometry-Based Protein Detection in SARS-CoV-2 Patients.

Rising population density and global mobility are among the reasons why pathogens such as SARS-CoV-2, the virus that causes COVID-19, spread so rapidly across the globe. The policy response to such pandemics will always have to include accurate monitoring of the spread, as this provides one of the few alternatives to total lockdown. However, COVID-19 diagnosis is currently performed almost exclusively by reverse transcription polymerase chain reaction (RT-PCR). Although this is efficient, automatable, and acceptably cheap, reliance on one type of technology comes with serious caveats, as illustrated by recurring reagent and test shortages. We therefore developed an alternative diagnostic test that detects proteolytically digested SARS-CoV-2 proteins using mass spectrometry (MS). We established the Cov-MS consortium, consisting of 15 academic laboratories and several industrial partners to increase applicability, accessibility, sensitivity, and robustness of this kind of SARS-CoV-2 detection. This, in turn, gave rise to the Cov-MS Digital Incubator that allows other laboratories to join the effort, navigate, and share their optimizations and translate the assay into their clinic. As this test relies on viral proteins instead of RNA, it provides an orthogonal and complementary approach to RT-PCR using other reagents that are relatively inexpensive and widely available, as well as orthogonally skilled personnel and different instruments. Data are available via ProteomeXchange with identifier PXD022550.

Intracranial hemorrhage in term newborns: management and outcomes.

Child neurology is frequently a late player in the management of the term newborn with intracranial hemorrhage in the first neonatal week. It is crucial, however, that the child neurologist undertake a comprehensive evaluation by investigating etiology and management of the hemorrhage. Intracranial hemorrhage is usually associated with premature newborns. The literature on intracranial hemorrhage in term newborns is largely in the form of isolated case reports or a small series of cases, and mostly nonsystematic. Presented here is an evidence-based review of the incidence, risk factors, etiologies, and clinical management of intracranial hemorrhage in the first week after birth, with discussion of the role of neuroimaging and hematologic investigation. Consideration of these investigations along with documentation of every intervention or its explanation will reduce parental anxiety and will assure the best possible neurologic as well as legal outcomes of term newborns with intracranial hemorrhage.

Intracranial incidental findings on brain MR images in a pediatric neurology practice: a retrospective study.

BACKGROUND AND PURPOSE: Previous studies have addressed the prevalence of incidental findings largely in healthy adult and pediatric populations. Our study aims to elucidate the prevalence of incidental findings in a pediatric neurology practice. METHODS: We reviewed the charts of 1618 patients seen at a pediatric neurology practice at a tertiary care center from September 2003 to December 2005 for clinical data and incidental intracranial findings on brain magnetic resonance imaging reports. Incidental findings were divided into two categories: normal or abnormal variants. Clinical and demographic data were assessed for associations with incidental findings. RESULTS: From 1618 charts reviewed, only 666 patients (41% of all patients) had brain MRIs ordered. One-hundred and seventy-one (171) patients (25.7% of all patients; 95% CI: 22.6, 29.0) had incidental findings. Of these, 113 (17.0%; 95% CI: 14.1, 19.8) were classified as normal-variants and 58 (8.7%; 95% CI: 6.6, 10.9) were classified as abnormal. The nature of incidental findings was not related to age group, sex or clinical diagnosis (p=0.29, p=0.31 and p=0.69 respectively). Two patients (0.3%; 95% CI: approximately 0.0, 0.7) required neurosurgical referral. CONCLUSIONS: We report a high prevalence of and a low rate of referrals for incidental findings in comparison to previous studies. The present study may help guide management decisions and discussions with patients and families. Future studies should attempt to address issues of associations between primary or secondary diagnoses and intracranial incidental findings in a controlled, prospective fashion.

Spinocerebellar ataxia type 7 mimicking Kearns-Sayre syndrome: a clinical diagnosis is desirable.

Spinocerebellar ataxias are a group of autosomal dominant cerebellar degenerative disorders, which are characterized by clinical and genetic variability. Spinocerebellar ataxia type 7 (SCA7) is less variable in clinical presentation than other SCAs. We present a pediatric patient with 13 and 70 trinucleotide CAG repeats within SCA7 gene and no family history, whose presentation mimicked Kearns-Sayre syndrome (KSS). We review the differential diagnosis of cerebellar ataxia with vision loss secondary to retinal pigmentary dystrophy. This paper supports concept of a desirable clinical diagnosis to avoid multiple genetic or invasive testing in children with neurodegenerative disorders.

Skin-impedance in Fabry Disease: a prospective, controlled, non-randomized clinical study.

BACKGROUND: We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system. METHODS: We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100th repetitive reading, 2) rate of change, 3) average of 60-110th reading and 4) overall average of all readings. RESULTS: All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions. CONCLUSION: The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.

Parietal bone defect: differential diagnosis and neurologic associations.

Parietal bone defects are rare and exhibit variable etiologies. We report on a 16-year-old girl with an isolated, giant parietal bone defect with encephalomalacia, and an asymptomatic Rathke's cleft cyst. The patient presented with epilepsy. We discuss the differential diagnosis and pertinent neurologic associations. Irrespective of cause, parietal bone defects remain a benign clinical entity. However, it is important to define the extent of the bone defect and associated intracranial abnormalities, and if needed, to take early preventive steps, medical as well as surgical, against potential brain damage.

Health-related quality of life using QOLIE-31: before and after epilepsy surgery a prospective study at a tertiary care center.

BACKGROUND: Outcome following epilepsy surgery has traditionally been measured in terms of relief of seizures. However, changes in health-related quality of life (HRQOL) after surgery for intractable epilepsy are also important to document. There are no studies on the Indian population which assess the outcome of epilepsy surgery in terms of HRQOL. MATERIALS AND METHODS: We conducted a prospective study on the patients undergoing epilepsy surgery for intractable seizures, between February 2004 and May 2006 at our center. All patients cleared for epilepsy surgery by the epilepsy surgery team were taken up for study. All patients RESULTS: Thirty-six patients satisfying the inclusion/exclusion criteria were included in the analysis. Twenty-nine of these (Group 1) had good seizure outcome (Engel 1 and 2), while seven patients (Group 2) had poor seizure outcome (Engel 3 and 4) at six months. Overall, 77% of all study patients were completely seizure-free at follow-up. There was no baseline difference in the seven domains of QOLIE-31 between the two groups. There was very significant improvement (P value>0.005 using paired sample T test) in all the domains of QOLIE-31 in the good outcome group after surgery. Health-related quality of life improvement was seen in all the domains in the poor outcome group also, however, it was statistically significant only for the following parameters: seizure worry, overall QOL, emotional wellbeing, energy fatigue and social functioning domains. Improvement in seizure worry, overall QOL, emotional wellbeing and social functioning was significantly more in Group 1 as compared to Group 2. CONCLUSION: Complete seizure-free state after surgery is associated with very significant improvement in HRQOL parameters. Several, but not all parameters of HRQOL as assessed by QOLIE-31, improved after surgery even in the poor seizure outcome group. The improvement in domains of seizure worry, overall QOL, emotional wellbeing and social functioning is significantly more in those patients in whom complete seizure-free state is achieved.

Spectrum of migraine variants and beyond: The individual syndromes in children.

"Migraine-related conditions" are probably the second most common condition after seizure encountered in pediatric neurology requiring frequent Emergency Department visits. Among migraines, migraine-related condition presents with an acute onset sign or symptom other than headache or visual aura of unknown etiology. A delay in diagnosis is a common occurrence. Previously, the authors proposed a common clinical profile and suggested that the future review should seek the applicability of the common profile in aid to clinical diagnosis of migraine-related individual syndromes. Authors describe the clinical characteristics and differential diagnosis of the spectrum of migraine variants and beyond in children.

Spectrum of intracranial incidental findings on pediatric brain magnetic resonance imaging: What clinician should know?

Intracranial incidental findings on magnetic resonance imaging (MRI) of the brain continue to generate interest in healthy control, research, and clinical subjects. However, in clinical practice, the discovery of incidental findings acts as a "distractor". This review is based on existing heterogeneous reports, their clinical implications, and how the results of incidental findings influence clinical management. This draws attention to the followings: (1) the prevalence of clinically significant incidental findings is low; (2) there is a lack of a systematic approach to classification; and discusses (3) how to deal with the detected incidental findings based a proposed common clinical profile. Individualized neurological care requires an active discussion regarding the need for neuroimaging. Clinical significance of incidental findings should be decided based on lesion's neuroradiologic characteristics in the given clinical context. Available evidence suggests that the outcome of an incidentally found "serious lesion in children" is excellent. Future studies of intracranial incidental findings on pediatric brain MRI should be focused on a homogeneous population. The study should address this clinical knowledge based review powered by the statistical analyses.

The relationship of vascular glycolipid storage to clinical manifestations of Fabry disease: a cross-sectional study of a large cohort of clinically affected heterozygous women.

Fabry disease is a rare X-linked lysosomal storage disorder caused by deficient activity of alpha-galactosidase A (alpha-Gal A) resulting in the storage of glycosphingolipids, especially globotriaosylceramide (Gb3), in cells throughout the body, causing life-threatening renal, cardiac, and cerebrovascular complications in hemizygous males and some heterozygous females. Disease manifestations in heterozygotes are being recognized increasingly, but quantitative prospective data on their extent and severity are limited. Prospective clinical and laboratory assessments were performed in a 7-day study of 61 women with signs and symptoms of Fabry disease. Analyses included medical history and physical, neurologic, cardiac, and ophthalmologic assessments; laboratory assessments; renal function tests; magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) of the head; and Fabry-related blood and urine tests, including Gb3 levels in blood and urine, skin biopsies, and DNA genotype analysis of the alpha-Gal A gene to identify causative mutations. Quality of life, pain and concomitant medication were documented using validated questionnaires and diaries. All patients had normal Gb3 levels in plasma; only 1 patient had visible storage material in the superficial dermal vascular endothelial cells. Cardiac, renal, or cerebrovascular abnormalities were documented in 52 of the 57 patients (91%) with confirmed Fabry genotypes. These included electrocardiographic abnormalities in 38 of 52 patients (73%), echocardiographic abnormalities in 8 of 57 (14%), proteinuria (>150 g protein/24-h urine) in 23 of 38 (61%), low estimated glomerular filtration rate (<90 mL/min per 1.73 m) in 24 of 57 (42%), abnormal MRI in 4 of 54 (7%), and abnormal MRA in 10 of 50 patients (20%). Angiokeratomas and corneal epitheliopathy were documented in 63% and 82% of the 57 patients, respectively. Despite the virtual absence of storage material in plasma and skin vascular endothelial cells, this population of women with Fabry disease exhibited a wide spectrum of clinical abnormalities. Useful outcome measures for assessment of specific therapies need to be developed. Studies limited to homogeneously affected subjects may be possible.

Spectrum of complicated migraine in children: A common profile in aid to clinical diagnosis.

Complicated migraine encompasses several individual clinical syndromes of migraine. Such a syndrome in children frequently presents with various neurological symptoms in the Emergency Department. An acute presentation in the absence of headache presents a diagnostic challenge. A delay in diagnosis and treatment may have medicolegal implication. To date, there are no reports of a common clinical profile proposed in making a clinical diagnosis for the complicated migraine. In this clinical review, we propose and describe: (1) A common clinical profile in aid to clinical diagnosis for spectrum of complicated migraine; (2) How it can be used in differentiating complicated migraine from migraine without aura, migraine with aura, and seizure; (3) We discuss the status of complicated migraine in the International Headache Society classification 2013; and (4) In addition, a common treatment strategy for the spectrum of migraine has been described. To diagnose complicated migraine clinically, it is imperative to adhere with the proposed profile. This will optimize the use of investigation and will also avoid a legal implication of delay in their management. The proposed common clinical profile is incongruent with the International Headache Society 2013. Future classification should minimize the dissociation from clinically encountered syndromes and coin a single word to address collectively this subtype of migraine with an acute presentation of a common clinical profile.