Data-driven learning of structure augments quantitative prediction of biological responses.

Multi-factor screenings are commonly used in diverse applications in medicine and bioengineering, including optimizing combination drug treatments and microbiome engineering. Despite the advances in high-throughput technologies, large-scale experiments typically remain prohibitively expensive. Here we introduce a machine learning platform, structure-augmented regression (SAR), that exploits the intrinsic structure of each biological system to learn a high-accuracy model with minimal data requirement. Under different environmental perturbations, each biological system exhibits a unique, structured phenotypic response. This structure can be learned based on limited data and once learned, can constrain subsequent quantitative predictions. We demonstrate that SAR requires significantly fewer data comparing to other existing machine-learning methods to achieve a high prediction accuracy, first on simulated data, then on experimental data of various systems and input dimensions. We then show how a learned structure can guide effective design of new experiments. Our approach has implications for predictive control of biological systems and an integration of machine learning prediction and experimental design.

Autoencoder neural networks enable low dimensional structure analyses of microbial growth dynamics.

The ability to effectively represent microbiome dynamics is a crucial challenge in their quantitative analysis and engineering. By using autoencoder neural networks, we show that microbial growth dynamics can be compressed into low-dimensional representations and reconstructed with high fidelity. These low-dimensional embeddings are just as effective, if not better, than raw data for tasks such as identifying bacterial strains, predicting traits like antibiotic resistance, and predicting community dynamics. Additionally, we demonstrate that essential dynamical information of these systems can be captured using far fewer variables than traditional mechanistic models. Our work suggests that machine learning can enable the creation of concise representations of high-dimensional microbiome dynamics to facilitate data analysis and gain new biological insights.

Legionella associated rhabdomyolysis: a case report.

BACKGROUND: Infections have been recognized as an uncommon cause of rhabdomyolysis, with evidence indicating a worse prognosis when compared to rhabdomyolysis caused by other etiologies. Diseases caused by Legionella pneumophila can present variably, ranging from mild to severe illness, as is sometimes the case with pneumonia. In particular, the triad of Legionnaire's disease, rhabdomyolysis, and acute kidney injury is associated with a significant increase in the morbidity and mortality, with most patients requiring initiation of renal replacement therapy such as hemodialysis. While the exact mechanism of both the muscle and kidney injury in this setting remains unknown, several hypotheses exist, with some research suggesting multiple yet distinct processes occurring in both target organs. CASE PRESENTATION: In this case report, we describe a 53-year-old African American man who presented with Legionella pneumophila pneumonia complicated by rhabdomyolysis and acute kidney injury. He was treated with aggressive fluid resuscitation and a 2-week course of azithromycin. His clinical status improved without necessitating renal replacement therapy or mechanical ventilation. We postulate that early recognition and treatment were key to his recovery. He was discharged 10 days later without recurrence of rhabdomyolysis at the time of this report. CONCLUSION: While there are several well-established and more common causes of rhabdomyolysis, clinicians should recognize Legionella sp. as an etiology, given its association with significant morbidity and mortality.

Vertical and horizontal gene transfer tradeoffs direct plasmid fitness.

Plasmid fitness is directed by two orthogonal processes-vertical transfer through cell division and horizontal transfer through conjugation. When considered individually, improvements in either mode of transfer can promote how well a plasmid spreads and persists. Together, however, the metabolic cost of conjugation could create a tradeoff that constrains plasmid evolution. Here, we present evidence for the presence, consequences, and molecular basis of a conjugation-growth tradeoff across 40 plasmids derived from clinical Escherichia coli pathogens. We discover that most plasmids operate below a conjugation efficiency threshold for major growth effects, indicating strong natural selection for vertical transfer. Below this threshold, E. coli demonstrates a remarkable growth tolerance to over four orders of magnitude change in conjugation efficiency. This tolerance fades as nutrients become scarce and horizontal transfer attracts a greater share of host resources. Our results provide insight into evolutionary constraints directing plasmid fitness and strategies to combat the spread of antibiotic resistance.

Temporal encoding of bacterial identity and traits in growth dynamics.

In biology, it is often critical to determine the identity of an organism and phenotypic traits of interest. Whole-genome sequencing can be useful for this but has limited power for trait prediction. However, we can take advantage of the inherent information content of phenotypes to bypass these limitations. We demonstrate, in clinical and environmental bacterial isolates, that growth dynamics in standardized conditions can differentiate between genotypes, even among strains from the same species. We find that for pairs of isolates, there is little correlation between genetic distance, according to phylogenetic analysis, and phenotypic distance, as determined by growth dynamics. This absence of correlation underscores the challenge in using genomics to infer phenotypes and vice versa. Bypassing this complexity, we show that growth dynamics alone can robustly predict antibiotic responses. These findings are a foundation for a method to identify traits not easily traced to a genetic mechanism.

Checks and Balances with Use of the Keio Collection for Phenotype Testing.

The Keio single gene knockout collection comprises approximately 4000 mutants of E. coli K12 strain BW25113, where each mutant contains a kanamycin resistance cassette in place of a single nonessential gene. This mutant library has proven to be incredibly useful in the fields of bacteriology, chemical genomics, biotechnology, and systems biology, which is evidenced by the greater than 3800 citations that the article describing its construction has garnered in the approximate first 11 years since its publication. Among the various applications of the collection, the most extensive use has been in the assessment of how loss of specific gene function influences phenotypes. In this chapter, we describe pitfalls with use of the collection and procedures that can be employed to ensure robust phenotype assessment of mutations in the library. These include procedures for thorough confirmation of gene deletions by PCR, phage transduction of mutated loci to new host strains, and strategies for genetic complementation.

Applying ecological resistance and resilience to dissect bacterial antibiotic responses.

An essential property of microbial communities is the ability to survive a disturbance. Survival can be achieved through resistance, the ability to absorb effects of a disturbance without a notable change, or resilience, the ability to recover after being perturbed by a disturbance. These concepts have long been applied to the analysis of ecological systems, although their interpretations are often subject to debate. Here, we show that this framework readily lends itself to the dissection of the bacterial response to antibiotic treatment, where both terms can be unambiguously defined. The ability to tolerate the antibiotic treatment in the short term corresponds to resistance, which primarily depends on traits associated with individual cells. In contrast, the ability to recover after being perturbed by an antibiotic corresponds to resilience, which primarily depends on traits associated with the population. This framework effectively reveals the phenotypic signatures of bacterial pathogens expressing extended-spectrum ß-lactamases (ESBLs) when treated by a ß-lactam antibiotic. Our analysis has implications for optimizing treatment of these pathogens using a combination of a ß-lactam and a ß-lactamase (Bla) inhibitor. In particular, our results underscore the need to dynamically optimize combination treatments based on the quantitative features of the bacterial response to the antibiotic or the Bla inhibitor.

Efficacy of Brain Gym Training on the Cognitive Performance and Fitness Level of Active Older Adults: A Preliminary Study.

This study evaluates the impact of Brain Gym (BG) training in active older adults. Eighty-five participants were assigned to four training groups: BG (n = 18), BG plus water-based exercise (n = 18), land-based exercise (n = 30), and land plus water-based exercise (n = 19). The effects of the programs on the attention and memory functions were assessed by means of the symbol digit modality test. The two-min step and the eight-foot up-and-go tests were used to evaluate their impact on fitness level. No program had a significant influence on the participant's cognitive performance, while different effects on the sample' fitness levels were observed. These findings suggest that the effects of BG on the cognitive performance and fitness level of active older adults are similar to those obtained after the practice of a traditional exercise program. Whether BG is performed in isolation or combined with other exercise programs seems to have no influence on such effects.

Position-specific anthropometry and throwing velocity of elite female water polo players.

This study was conducted with the following aims: (a) to describe the effect of playing position on anthropometrics and throwing velocity in elite female water polo players and (b) to observe any relationships between anthropometric parameters and throwing velocity. To achieve these aims, we analyzed a total of 46 female elite players (age: 22.5 ± 5.1 years; height: 172.0 ± 6.9 cm, body mass: 67.4 ± 7.5 kg) members of the top 4 teams of the Spanish Honour Division women league (21 offensive wings players, 17 center, and 8 goalkeepers). Wings were significantly shorter and had smaller arm spans than goalkeepers and center players. Goalkeepers demonstrated longer forearm lengths than wing and center players. No other significant differences were evident between positions in terms of anthropometric, strength, or throwing velocity variables The somatotype of the offensive wing players was mesomorphic, whereas centers were endomorph (classified as endomesomorphic). Height, arm span, muscular mass, biepicondylar breadth of the humerus, arm girth (relaxed and tensed), and forearm girth were related to throwing velocity. In conclusion, only a small number of anthropometric differences exist between players of different positions in elite female water polo. Shorter players with smaller arm spans may be better suited to the wings, whereas athletes with longer forearms may be better suited to the goalkeeper position. Taller, more muscular athletes with wider arm spans, broader humeri, and wider arms (relaxed and flexed) tended to throw with increased velocity. Trainers should focus on increasing the modifiable characteristics (muscle mass and arm girths) that contribute to throwing velocity in this population.

Dermatoglifos en el sindrome de Turner / Dermatoglyphics in the Turner's syndrome

Se presentan los resultados obtenidos en el estudio dermatoglífico de una serie de pacientes portadores del síndrome de Turner. Se comprueba el conteo total de crestas digitales: elevado, el de crestas en la linea ab:elevado y ángulo atd: aumentado en más de la mitad de los pacientes (77,5 por ciento, 67,5 por ciento y 51,6 por ciento, respectivamente). Otros hallazgos frecuentes fueron: predominio de rizos o azas cubitales y patrones en I3 e I4 en el 41,9 por ciento así como trirradio axial distal y patrones hipotenares en el 38,7por ciento. Se señala que según los resultados obtenidos, este examen es útil enel diagnóstico de este síndrome. Los pacientes con dermatoglifos menos típicos presentaron cariotípo distinto a 45,X (AU)