Ranked Adjusted Rand: integrating distance and partition information in a measure of clustering agreement

BACKGROUND: Biological information is commonly used to cluster or classify entities of interest such as genes, conditions, species or samples. However, different sources of data can be used to classify the same set of entities and methods allowing the comparison of the performance of two data sources or the determination of how well a given classification agrees with another are frequently needed, especially in the absence of a universally accepted "gold standard" classification. RESULTS: Here, we describe a novel measure – the Ranked Adjusted Rand (RAR) index. RAR differs from existing methods by evaluating the extent of agreement between any two groupings, taking into account the intercluster distances. This characteristic is relevant to evaluate cases of pairs of entities grouped in the same cluster by one method and separated by another. The latter method may assign them to close neighbour clusters or, on the contrary, to clusters that are far apart from each other. RAR is applicable even when intercluster distance information is absent for both or one of the groupings. In the first case, RAR is equal to its predecessor, Adjusted Rand (HA) index. Artificially designed clusterings were used to demonstrate situations in which only RAR was able to detect differences in the grouping patterns. A study with larger simulated clusterings ensured that in realistic conditions, RAR is effectively integrating distance and partition information. The new method was applied to biological examples to compare 1) two microbial typing methods, 2) two gene regulatory network distances and 3) microarray gene expression data with pathway information. In the first application, one of the methods does not provide intercluster distances while the other originated a hierarchical clustering. RAR proved to be more sensitive than HA in the choice of a threshold for defining clusters in the hierarchical method that maximizes agreement between the results of both methods. CONCLUSION: RAR has its major advantage in combining cluster distance and partition information, while the previously available methods used only the latter. RAR should be used in the research problems were HA was previously used, because in the absence of inter cluster distance effects it is an equally effective measure, and in the presence of distance effects it is a more complete one

Axonal Regeneration and Neuronal Function Are Preserved in Motor Neurons Lacking ß-Actin In Vivo

The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA), suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO) to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo

Prediction of disability-free survival in healthy older people

Prolonging survival in good health is a fundamental societal goal. However, the leading determinants of disability-free survival in healthy older people have not been well established. Data from ASPREE, a bi-national placebo-controlled trial of aspirin with 4.7 years median follow-up, was analysed. At enrolment, participants were healthy and without prior cardiovascular events, dementia or persistent physical disability. Disability-free survival outcome was defined as absence of dementia, persistent disability or death. Selection of potential predictors from amongst 25 biomedical, psychosocial and lifestyle variables including recognized geriatric risk factors, utilizing a machine-learning approach. Separate models were developed for men and women. The selected predictors were evaluated in a multivariable Cox proportional hazards model and validated internally by bootstrapping. We included 19,114 Australian and US participants aged ≥65 years (median 74 years, IQR 71.6–77.7). Common predictors of a worse prognosis in both sexes included higher age, lower Modified Mini-Mental State Examination score, lower gait speed, lower grip strength and abnormal (low or elevated) body mass index. Additional risk factors for men included current smoking, and abnormal eGFR. In women, diabetes and depression were additional predictors. The biased-corrected areas under the receiver operating characteristic curves for the final prognostic models at 5 years were 0.72 for men and 0.75 for women. Final models showed good calibration between the observed and predicted risks. We developed a prediction model in which age, cognitive function and gait speed were the strongest predictors of disability-free survival in healthy older people. Trial registration Clinicaltrials.gov (NCT01038583

Operator Centered Design of Ship Systems

Cognitive science research, much of it supported by the Office of Naval Research, is bringing about a scientific revolution in our understanding of the human operator. It is yielding computational theories of human cognition and perceptual/motor activity that provide precise quantitative predictions of important variables such as the times required to complete tasks or to learn them in training. Although the scope of coverage of these theories is limited and basic research aimed at expanding them is on-going, they already have much to offer in aiding the design of ship systems that will optimize the combined effectiveness of human operators and the systems they will be using. This presentation discusses 1) what can be done now, 2) tools under development that will facilitate the use of these theories, reducing the labor involved, and 3) a long-term vision for what might be achieved in this area