LipidFinder 2.0: advanced informatics pipeline for lipidomics discovery applications.

SUMMARY: We present LipidFinder 2.0, incorporating four new modules that apply artefact filters, remove lipid and contaminant stacks, in-source fragments and salt clusters, and a new isotope deletion method which is significantly more sensitive than available open-access alternatives. We also incorporate a novel false discovery rate method, utilizing a target-decoy strategy, which allows users to assess data quality. A renewed lipid profiling method is introduced which searches three different databases from LIPID MAPS and returns bulk lipid structures only, and a lipid category scatter plot with color blind friendly pallet. An API interface with XCMS Online is made available on LipidFinder's online version. We show using real data that LipidFinder 2.0 provides a significant improvement over non-lipid metabolite filtering and lipid profiling, compared to available tools. AVAILABILITY AND IMPLEMENTATION: LipidFinder 2.0 is freely available at https://github.com/ODonnell-Lipidomics/LipidFinder and http://lipidmaps.org/resources/tools/lipidfinder. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

LipidFinder on LIPID MAPS: peak filtering, MS searching and statistical analysis for lipidomics.

SUMMARY: We present LipidFinder online, hosted on the LIPID MAPS website, as a liquid chromatography/mass spectrometry (LC/MS) workflow comprising peak filtering, MS searching and statistical analysis components, highly customized for interrogating lipidomic data. The online interface of LipidFinder includes several innovations such as comprehensive parameter tuning, a MS search engine employing in-house customized, curated and computationally generated databases and multiple reporting/display options. A set of integrated statistical analysis tools which enable users to identify those features which are significantly-altered under the selected experimental conditions, thereby greatly reducing the complexity of the peaklist prior to MS searching is included. LipidFinder is presented as a highly flexible, extensible user-friendly online workflow which leverages the lipidomics knowledge base and resources of the LIPID MAPS website, long recognized as a leading global lipidomics portal. AVAILABILITY AND IMPLEMENTATION: LipidFinder on LIPID MAPS is available at: http://www.lipidmaps.org/data/LF.

Correction to: Timing rather than user traits mediates mood sampling on smartphones.

An amendment to this paper has been published and can be accessed via the original article.

Metabolic Dysregulation of the Lysophospholipid/Autotaxin Axis in the Chromosome 9p21 Gene SNP rs10757274.

BACKGROUND: Common chromosome 9p21 single nucleotide polymorphisms (SNPs) increase coronary heart disease risk, independent of traditional lipid risk factors. However, lipids comprise large numbers of structurally related molecules not measured in traditional risk measurements, and many have inflammatory bioactivities. Here, we applied lipidomic and genomic approaches to 3 model systems to characterize lipid metabolic changes in common Chr9p21 SNPs, which confer ≈30% elevated coronary heart disease risk associated with altered expression of ANRIL, a long ncRNA. METHODS: Untargeted and targeted lipidomics was applied to plasma from NPHSII (Northwick Park Heart Study II) homozygotes for AA or GG in rs10757274, followed by correlation and network analysis. To identify candidate genes, transcriptomic data from shRNA downregulation of ANRIL in HEK-293 cells was mined. Transcriptional data from vascular smooth muscle cells differentiated from induced pluripotent stem cells of individuals with/without Chr9p21 risk, nonrisk alleles, and corresponding knockout isogenic lines were next examined. Last, an in-silico analysis of miRNAs was conducted to identify how ANRIL might control lysoPL (lysophosphospholipid)/lysoPA (lysophosphatidic acid) genes. RESULTS: Elevated risk GG correlated with reduced lysoPLs, lysoPA, and ATX (autotaxin). Five other risk SNPs did not show this phenotype. LysoPL-lysoPA interconversion was uncoupled from ATX in GG plasma, suggesting metabolic dysregulation. Significantly altered expression of several lysoPL/lysoPA metabolizing enzymes was found in HEK cells lacking ANRIL. In the vascular smooth muscle cells data set, the presence of risk alleles associated with altered expression of several lysoPL/lysoPA enzymes. Deletion of the risk locus reversed the expression of several lysoPL/lysoPA genes to nonrisk haplotype levels. Genes that were altered across both cell data sets were DGKA, MBOAT2, PLPP1, and LPL. The in-silico analysis identified 4 ANRIL-regulated miRNAs that control lysoPL genes as miR-186-3p, miR-34a-3p, miR-122-5p, and miR-34a-5p. CONCLUSIONS: A Chr9p21 risk SNP associates with complex alterations in immune-bioactive phospholipids and their metabolism. Lipid metabolites and genomic pathways associated with coronary heart disease pathogenesis in Chr9p21 and ANRIL-associated disease are demonstrated.

Identifying Indicators of Smartphone Addiction Through User-App Interaction.

We introduce a new approach to monitoring the activity of smartphone users based on their physical interactions with the interface. Typical events are taps, scrolling and typing, carried out to interact with apps. As compared to other measures, this directly encapsulates potential problematic physical smartphone behaviour as a signal. The approach contrasts against conventions such as self-reporting or timing activity sessions, and it focusses on active rather than passive smartphone activity. Using this alternative method, we collected all user interface interaction events from a sample of 64 participants over a period of 8 weeks, using a bespoke monitoring app called Tymer. User Smartphone Addiction was seen to significantly correlate with high levels of interaction with Lifestyle apps, particularly for female users. Interactions with Social apps in general were also associated with Smartphone Addiction. In particular, user interactions with Snapchat correlated with Smartphone Addiction, represented across all types of interface interaction. This is significant given the widespread usage of Snapchat by teenagers, and we hypothesise that the app's design provides a particularly strong pathway in support of Smartphone Addiction.

Evidence to support common application switching behaviour on smartphones.

We find evidence to support common behaviour in smartphone usage based on analysis of application (app) switching. This is an overlooked aspect of smartphone usage that gives additional insight beyond screen time and the particular apps that are accessed. Using a dataset of usage behaviour from 53 participants over a six-week period, we find strong similarity in the structure of networks built from app switching, despite diversity in the apps used, and the volume of app switching. App switch networks exhibit small-world, broad-scale network features, with a rapid popularity decay, suggesting that preferential attachment may drive next-app decision-making.

Personality Homophily and Geographic Distance in Facebook.

Personality homophily remains an understudied aspect of social networks, with the traditional focus concerning sociodemographic variables as the basis for assortativity, rather than psychological dispositions. We consider the effect of personality homophily on one of the biggest constraints to human social networks: geographic distance. We use the Big Five model of personality to make predictions for each of the five facets: Openness to experience, Conscientiousness, Extraversion, Agreeableness, and Neuroticism. Using a network of 313,669 Facebook users, we investigate the difference in geographic distance between homophilous pairs, in which both users scored similarly on a particular facet, and mixed pairs. In accordance with our hypotheses, we find that pairs of open and conscientious users are geographically further apart than mixed pairs. Pairs of extraverts, on the other hand, tend to be geographically closer together. We find mixed results for the Neuroticism facet, and no significant effects for the Agreeableness facet. The results are discussed in the context of personality homophily and the impact of geographic distance on social connections.

Timing rather than user traits mediates mood sampling on smartphones.

OBJECTIVE: Recent years have seen an increasing number of studies using smartphones to sample participants' mood states. Moods are usually collected by asking participants for their current mood or for a recollection of their mood states over a specific period of time. The current study investigates the reasons to favour collecting mood through current or daily mood surveys and outlines design recommendations for mood sampling using smartphones based on these findings. These recommendations are also relevant to more general smartphone sampling procedures. RESULTS: N=64 participants completed a series of surveys at the beginning and end of the study providing information such as gender, personality, or smartphone addiction score. Through a smartphone application, they reported their current mood 3 times and daily mood once per day for 8 weeks. We found that none of the examined intrinsic individual qualities had an effect on matches of current and daily mood reports. However timing played a significant role: the last followed by the first reported current mood of the day were more likely to match the daily mood. Current mood surveys should be preferred for a higher sampling accuracy, while daily mood surveys are more suitable if compliance is more important.

LipidFinder: A computational workflow for discovery of lipids identifies eicosanoid-phosphoinositides in platelets.

Accurate and high-quality curation of lipidomic datasets generated from plasma, cells, or tissues is becoming essential for cell biology investigations and biomarker discovery for personalized medicine. However, a major challenge lies in removing artifacts otherwise mistakenly interpreted as real lipids from large mass spectrometry files (>60 K features), while retaining genuine ions in the dataset. This requires powerful informatics tools; however, available workflows have not been tailored specifically for lipidomics, particularly discovery research. We designed LipidFinder, an open-source Python workflow. An algorithm is included that optimizes analysis based on users' own data, and outputs are screened against online databases and categorized into LIPID MAPS classes. LipidFinder outperformed three widely used metabolomics packages using data from human platelets. We show a family of three 12-hydroxyeicosatetraenoic acid phosphoinositides (16:0/, 18:1/, 18:0/12-HETE-PI) generated by thrombin-activated platelets, indicating crosstalk between eicosanoid and phosphoinositide pathways in human cells. The software is available on GitHub (https://github.com/cjbrasher/LipidFinder), with full userguides.

A Dominant Social Comparison Heuristic Unites Alternative Mechanisms for the Evolution of Indirect Reciprocity.

Cooperation is a fundamental human trait but our understanding of how it functions remains incomplete. Indirect reciprocity is a particular case in point, where one-shot donations are made to unrelated beneficiaries without any guarantee of payback. Existing insights are largely from two independent perspectives: i) individual-level cognitive behaviour in decision making, and ii) identification of conditions that favour evolution of cooperation. We identify a fundamental connection between these two areas by examining social comparison as a means through which indirect reciprocity can evolve. Social comparison is well established as an inherent human disposition through which humans navigate the social world by self-referential evaluation of others. Donating to those that are at least as reputable as oneself emerges as a dominant heuristic, which represents aspirational homophily. This heuristic is found to be implicitly present in the current knowledge of conditions that favour indirect reciprocity. The effective social norms for updating reputation are also observed to support this heuristic. We hypothesise that the cognitive challenge associated with social comparison has contributed to cerebral expansion and the disproportionate human brain size, consistent with the social complexity hypothesis. The findings have relevance for the evolution of autonomous systems that are characterised by one-shot interactions.

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation.

Human platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via ß-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented.