A flexible framework for sparse simultaneous component based data integration

<p>Abstract</p> <p>1 Background</p> <p>High throughput data are complex and methods that reveal structure underlying the data are most useful. Principal component analysis, frequently implemented as a singular value decomposition, is a popular technique in this respect. Nowadays often the challenge is to reveal structure in several sources of information (e.g., transcriptomics, proteomics) that are available for the same biological entities under study. Simultaneous component methods are most promising in this respect. However, the interpretation of the principal and simultaneous components is often daunting because contributions of each of the biomolecules (transcripts, proteins) have to be taken into account.</p> <p>2 Results</p> <p>We propose a sparse simultaneous component method that makes many of the parameters redundant by shrinking them to zero. It includes principal component analysis, sparse principal component analysis, and ordinary simultaneous component analysis as special cases. Several penalties can be tuned that account in different ways for the block structure present in the integrated data. This yields known sparse approaches as the lasso, the ridge penalty, the elastic net, the group lasso, sparse group lasso, and elitist lasso. In addition, the algorithmic results can be easily transposed to the context of regression. Metabolomics data obtained with two measurement platforms for the same set of <it>Escherichia coli </it>samples are used to illustrate the proposed methodology and the properties of different penalties with respect to sparseness across and within data blocks.</p> <p>3 Conclusion</p> <p>Sparse simultaneous component analysis is a useful method for data integration: First, simultaneous analyses of multiple blocks offer advantages over sequential and separate analyses and second, interpretation of the results is highly facilitated by their sparseness. The approach offered is flexible and allows to take the block structure in different ways into account. As such, structures can be found that are exclusively tied to one data platform (group lasso approach) as well as structures that involve all data platforms (Elitist lasso approach).</p> <p>4 Availability</p> <p>The additional file contains a MATLAB implementation of the sparse simultaneous component method.</p

Placebo Effects in the Neuroendocrine System: Conditioning of the Oxytocin Responses

OBJECTIVE: There is evidence that placebo effects may influence hormone secretion. However, few studies have examined placebo effects in the endocrine system, including oxytocin placebo effects. We studied whether it is possible to trigger oxytocin placebo effects using a classical conditioning paradigm. METHODS: Ninety-nine women were assigned to a conditioned, control, or drug control group. In the two-phase conditioning paradigm, participants in the conditioned and drug control groups received an oxytocin nasal spray combined with a distinctive smell (conditioned stimulus [CS]) for three acquisition days, whereas the control group received placebo spray. Subsequently, the conditioned and control groups received placebo spray with the CS and the drug control group received oxytocin spray for three evocation days. Salivary oxytocin was measured several times during each day. Pain sensitivity and facial evaluation tests previously used in oxytocin research were also administered. RESULTS: On evocation day 1, in the conditioned group, oxytocin significantly increased from baseline to 5 minutes after CS (B[slope] = 19.55, SE = 5.88, p < .001) and remained increased from 5 to 20 (B = -10.42, SE = 5.81, p = .071) and 50 minutes (B = -0.70, SE = 3.37, p = .84). On evocation day 2, a trend for increase in oxytocin was found at 5 minutes (B = 15.22, SE = 8.14, p = .062). No placebo effect was found on evocation day 3 (B = 3.57, SE = 3.26, p = .28). Neither exogenous nor conditioned oxytocin affected pain or facial tasks. CONCLUSIONS: Results indicate that oxytocin release can be conditioned and that this response extinguishes over time. Triggering hormonal release by placebo manipulation offers various clinical possibilities, such as enhancing effects of pharmacological treatments or reducing dosages of medications. TRIAL REGISTRATION: The study was registered as a clinical trial on www.trialregister.nl (number NTR5596)

Neurobiological correlates of antisociality across adolescence and young adulthood: a multi-sample, multi-method study

Background Antisociality across adolescence and young adulthood puts individuals at high risk of developing a variety of problems. Prior research has linked antisociality to autonomic nervous system and endocrinological functioning. However, there is large heterogeneity in antisocial behaviors, and these neurobiological measures are rarely studied conjointly, limited to small specific studies with narrow age ranges, and yield mixed findings due to the type of behavior examined. Methods We harmonized data from 1489 participants (9-27 years, 67% male), from six heterogeneous samples. In the resulting dataset, we tested relations between distinct dimensions of antisociality and heart rate, pre-ejection period (PEP), respiratory sinus arrhythmia, respiration rate, skin conductance levels, testosterone, basal cortisol, and the cortisol awakening response (CAR), and test the role of age throughout adolescence and young adulthood. Results Three dimensions of antisociality were uncovered: 'callous-unemotional (CU)/manipulative traits', 'intentional aggression/conduct', and 'reactivity/impulsivity/irritability'. Shorter PEPs and higher testosterone were related to CU/manipulative traits, and a higher CAR is related to both CU/manipulative traits and intentional aggression/conduct. These effects were stable across age. Conclusions Across a heterogeneous sample and consistent across development, the CAR may be a valuable measure to link to CU/manipulative traits and intentional aggression, while sympathetic arousal and testosterone are additionally valuable to understand CU/manipulative traits. Together, these findings deepen our understanding of the fundamental mechanisms underlying different components of antisociality. Finally, we illustrate the potential of using current statistical techniques for combining multiple datasets to draw robust conclusions about biobehavioral associations

Heart work after errors: Behavioral adjustment following error commission involves cardiac effort

Posterror slowing (PES) is the observation that people respond slower on trials subsequent to error commissions than on trials subsequent to correct responses. Different accounts have been proposed to explain PES. On the one hand, it has been suggested that PES arises from an adaptive increase in cognitive control following error commission, thereby making people more cautious after making an error. On the other hand, PES has been attributed to an orienting response, indicating that attention is shifted toward the error. In the present study we tested these accounts by investigating the effects of error commission in both flanker and switch tasks on two task-evoked cardiac measures: the interbeat interval-that is, the interval between two consecutive R peaks-and the RZ interval-that is, the interval between the R peak and the Z point-as measured using electro- and impedance cardiography, respectively. These measures allowed us to measure cardiac deceleration (autonomic orienting) and cardiac effort mobilization, respectively. Our results revealed a shorter RZ interval during posterror trials, indicating increased effort mobilization following errors. In addition, we replicated earlier studies that have shown cardiac slowing during error trials. However, multilevel analyses showed that only the posterror decrease in RZ interval predicted posterror reaction times, whereas there was no positive relationship between error-related cardiac deceleration and posterror reaction times. Our results suggest that PES is related to increased cardiac effort, supporting a cognitive-control account of PES.status: publishe

Heart work after errors: Behavioral adjustment following error commission involves cardiac effort

Posterror slowing (PES) is the observation that people respond slower on trials subsequent to error commissions than on trials subsequent to correct responses. Different accounts have been proposed to explain PES. On the one hand, it has been suggested that PES arises from an adaptive increase in cognitive control following error commission, thereby making people more cautious after making an error. On the other hand, PES has been attributed to an orienting response, indicating that attention is shifted toward the error. In the present study we tested these accounts by investigating the effects of error commission in both flanker and switch tasks on two task-evoked cardiac measures: the interbeat interval—that is, the interval between two consecutive R peaks—and the RZ interval—that is, the interval between the R peak and the Z point—as measured using electro- and impedance cardiography, respectively. These measures allowed us to measure cardiac deceleration (autonomic orienting) and cardiac effort mobilization, respectively. Our results revealed a shorter RZ interval during posterror trials, indicating increased effort mobilization following errors. In addition, we replicated earlier studies that have shown cardiac slowing during error trials. However, multilevel analyses showed that only the posterror decrease in RZ interval predicted posterror reaction times, whereas there was no positive relationship between error-related cardiac deceleration and posterror reaction times. Our results suggest that PES is related to increased cardiac effort, supporting a cognitive-control account of PES.</p