Domain-invariant features for mechanism of action prediction in a multi-cell-line drug screen.

MOTIVATION: High-content screening is an important tool in drug discovery and characterization. Often, high-content drug screens are performed on one single-cell line. Yet, a single-cell line cannot be thought of as a perfect disease model. Many diseases feature an important molecular heterogeneity. Consequently, a drug may be effective against one molecular subtype of a disease, but less so against another. To characterize drugs with respect to their effect not only on one cell line but on a panel of cell lines is therefore a promising strategy to streamline the drug discovery process. RESULTS: The contribution of this article is 2-fold. First, we investigate whether we can predict drug mechanism of action (MOA) at the molecular level without optimization of the MOA classes to the screen specificities. To this end, we benchmark a set of algorithms within a conventional pipeline, and evaluate their MOA prediction performance according to a statistically rigorous framework. Second, we extend this conventional pipeline to the simultaneous analysis of multiple cell lines, each manifesting potentially different morphological baselines. For this, we propose multi-task autoencoders, including a domain-adaptive model used to construct domain-invariant feature representations across cell lines. We apply these methods to a pilot screen of two triple negative breast cancer cell lines as models for two different molecular subtypes of the disease. AVAILABILITY AND IMPLEMENTATION: https://github.com/jcboyd/multi-cell-line or https://zenodo.org/record/2677923. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Sodium bicarbonate supplementation improves hypertrophy-type resistance exercise performance.

The aim of the present study was to examine the effects of sodium bicarbonate (NaHCO(3)) administration on lower-body, hypertrophy-type resistance exercise (HRE). Using a double-blind randomized counterbalanced design, 12 resistance-trained male participants (mean ± SD; age = 20.3 ± 2 years, mass = 88.3 ± 13.2 kg, height = 1.80 ± 0.07 m) ingested 0.3 g kg(-1) of NaHCO(3) or placebo 60 min before initiation of an HRE regimen. The protocol employed multiple exercises: squat, leg press, and knee extension, utilizing four sets each, with 10-12 repetition-maximum loads and short rest periods between sets. Exercise performance was determined by total repetitions generated during each exercise, total accumulated repetitions, and a performance test involving a fifth set of knee extensions to failure. Arterialized capillary blood was collected via fingertip puncture at four time points and analyzed for pH, [HCO(3)(-)], base excess (BE), and lactate [Lac(-)]. NaHCO(3) supplementation induced a significant alkaline state (pH: NaHCO(3): 7.49 ± 0.02, placebo: 7.42 ± 0.02, P < 0.05; [HCO(3)(-)]: NaHCO(3): 31.50 ± 2.59, placebo: 25.38 ± 1.78 mEq L(-1), P < 0.05; BE: NaHCO(3): 7.92 ± 2.57, placebo: 1.08 ± 2.11 mEq L(-1), P < 0.05). NaHCO(3) administration resulted in significantly more total repetitions than placebo (NaHCO(3): 139.8 ± 13.2, placebo: 134.4 ± 13.5), as well as significantly greater blood [Lac(-)] after the exercise protocol (NaHCO(3): 17.92 ± 2.08, placebo: 15.55 ± 2.50 mM, P < 0.05). These findings demonstrate ergogenic efficacy for NaHCO(3) during HRE and warrant further investigation into chronic training applications.

The effect of glycerol on torque, electromyography, and mechanomyography.

The purpose of this investigation was to determine the effect of hyperhydration on the electromyographic (EMG) and mechanomyographic (MMG) responses during isometric and isokinetic muscle actions of the biceps brachii. Eight (22.1 +/- 1.8 years, 79.5 +/- 22.8 kg) subjects were tested for maximal isometric, submaximal isometric, and maximal concentric isokinetic muscle strength in either a control (C) or hyperhydrated (H) state induced by glycerol ingestion while the EMG and MMG signals were recorded. Although fluid retention was significantly greater during the H protocol, the analyses indicated no change in torque, EMG amplitude, EMG mean power frequency (MPF), MMG amplitude, or MMG MPF with hyperhydration. These results indicated that glycerol-induced fluid retention does not affect the torque-producing capabilities of a muscle, the impulses (EMG) going to a muscle, or muscular vibrations (MMG). It has been suggested that EMG and MMG can be used as direct electrical/mechanical monitoring, which could be presented to trainers and athletes; however, before determining the utility of these signals, the MMG and EMG responses should be examined under a variety of conditions such as in the present study.

Comparison of glycerol and water hydration regimens on tennis-related performance.

PURPOSE: To compare glycerol and water hyperhydration and rehydration on tennis related skill and agility performance. METHODS: Eleven male subjects completed two counter-balanced, double-blind trials. Each trial consisted of three phases: 1). hyperhydration with or without glycerol (1.0 g.kg/(-1)) over 150 min, 2). 120 min of exercise-induced dehydration (EID), and 3) rehydration with or without glycerol (0.5 g.kg(-1)) over 90 min. After each phase, subjects performed 5- and 10-m sprint tests, a repeated-effort agility test, and tennis skill tests. RESULTS: Glycerol (G) hyperhydration significantly increased fluid retention by approximately 900 mL over the placebo (P) (P

Effect of moderate dehydration on torque, electromyography, and mechanomyography.

The purpose of the present investigation was to test the hypotheses that the mechanomyographic (MMG) signal would be affected by hydration status due to changes in the intra- and extracellular fluid content (which could affect the degree of fluid turbulence), changes in the filtering properties of the tissues between the MMG sensor and muscle, and changes in torque production that may accompany dehydration. Ten subjects (age 22.5 +/- 1.6 years) were tested for maximal isometric (MVC), submaximal isometric (25, 50, and 75%MVC), and maximal concentric isokinetic muscle strength of the biceps brachii in either a euhydrated or dehydrated state while the electromyographic (EMG) and MMG signals were recorded. Separate three-way and two-way ANOVAs indicated no change in torque, EMG amplitude, EMG mean power frequency (MPF), MMG amplitude, and MMG MPF with dehydration. The lack of dehydration effect suggests that MMG may be more reflective of the intrinsic contractile processes of a muscle fiber (torque production) or the motor control mechanisms (reflected by the EMG) than the tissues and fluids surrounding the muscle fiber.