SIDEKICK: Genomic data driven analysis and decision-making framework

Background  

Scientists striving to unlock mysteries within complex biological systems face myriad barriers in effectively integrating available information to enhance their understanding. While experimental techniques and available data sources are rapidly evolving, useful information is dispersed across a variety of sources, and sources of the same information often do not use the same format or nomenclature. To harness these expanding resources, scientists need tools that bridge nomenclature differences and allow them to integrate, organize, and evaluate the quality of information without extensive computation.     

Using patient and physician perspectives to develop a shared decision-making framework for colorectal cancer

The Quality Enhancement Research Initiative (QUERI) program and implementation research have both come of age in the 10 years since QUERI was established. Looking forward, if QUERI and the field of implementation science are to mature successfully, we will need to address a series of challenges. First, we need to more clearly demonstrate how applying principles of implementation science leads to more effective implementation and communicate those lessons to our partners and funders. Second, we will need to engage in the ongoing debate over methodological standards in quality improvement and implementation research. Third, a program like QUERI needs to become more relevant to the daily decisions of key stakeholders. Fourth, if we hope to sustain interest in implementation science, we will need to demonstrate the business case for more effective implementation. Fifth, we need to think creatively about how to nurture the next generations of implementation researchers and front-line "connectors," who are critical for accelerating implementation. Finally, we need to strengthen the connections between implementation research and the other operational and research activities that influence change in healthcare systems. The excitement of entering adulthood is tempered by the challenge of new responsibilities and expectations. What is essential is that we continue to learn and move forward. For implementation science and for QUERI, the next decade looks to be one filled with exciting possibilities, new partnerships, increasing relevance, and real accomplishment.     

Secondary metabolism, inventive evolution and biochemical diversity--a review.

Evidence now being obtained through nucleotide (nt) sequence analysis supports the concept that secondary metabolism has arisen by modification of existing primary metabolic reactions. Although amino acid sequence identity deduced from nt sequences of genes encoding proteins from related primary and secondary metabolic pathways is sufficient to indicate a common ancestry, the match is often better when genes in different rather than in the same species are compared. The information so far available suggests that gene transfer between organisms has been an important factor in the evolution of secondary metabolism. Many secondary pathways may be of relatively ancient origin and they may have arisen only infrequently. Much subsequent elaboration of the pathways has probably taken place after their acquisition by other species and so has been influenced by a variety of selective conditions. The characteristic diversity of secondary metabolites and their functions can be accounted for by the random manner in which the pathways initially evolved and have subsequently been exploited.     

Liberal rationalism and medical decision-making

I contrast Robert Veatch's recent liberal vision of medical decision-making with a more rationalist liberal model. According to Veatch, physicians are biased in their determination of what is in their patient's overall interests in favour of their medical interests. Because of the extent of this bias, we should abandon the practice of physicians offering what they guess to be the best treatment option. Patients should buddy up with physicians who share the same values —'deep value pairing'. The goal of choice is maximal promotion of patient values. I argue that if subjectivism about value and valuing is true, this move is plausible. However, if objectivism about value is true — that there really are states which are good for people regardless of whether they desire to be in them — then we should accept a more rationalist liberal alternative. According to this alternative, what is required to decide which course is best is rational dialogue between physicians and patients, both about the patient's circumstances and her values, and not the seeking out of people, physicians or others, who share the same values. Rational discussion requires that physicians be reasonable and empathic. I describe one possible account of a reasonable physician.     

Patient decision-making capacity and risk

Although certain requisites of patient decision-making competency are generally agreed upon, there is no universally recognized standard. Wicclair, of the University of West Virginia Department of Philosophy, offers two reasons why a single standard should not be determined. First, competency is variable according to the decision at hand, i.e., task-related. Second, arguments in support of risk-related criteria fail. Wicclair challenges claims that a risk-related standard is legally the most feasible, is supported by the doctrine of informed consent, is consistent with everyday competence judgments, and achieves the best compromise between patient autonomy and concern for patient well-being. He argues that where risk is high, such a standard threatens unattainable requirements for competency; and where it is low, offers no set minimum, resulting in overly weak competency standards. Wicclair concludes that the standard of decision-making capacity should not vary by risk perceived.     

Continuous evolution of statistical estimators for optimal decision-making

In many everyday situations, humans must make precise decisions in the presence of uncertain sensory information. For example, when asked to combine information from multiple sources we often assign greater weight to the more reliable information. It has been proposed that statistical-optimality often observed in human perception and decision-making requires that humans have access to the uncertainty of both their senses and their decisions. However, the mechanisms underlying the processes of uncertainty estimation remain largely unexplored. In this paper we introduce a novel visual tracking experiment that requires subjects to continuously report their evolving perception of the mean and uncertainty of noisy visual cues over time. We show that subjects accumulate sensory information over the course of a trial to form a continuous estimate of the mean, hindered only by natural kinematic constraints (sensorimotor latency etc.). Furthermore, subjects have access to a measure of their continuous objective uncertainty, rapidly acquired from sensory information available within a trial, but limited by natural kinematic constraints and a conservative margin for error. Our results provide the first direct evidence of the continuous mean and uncertainty estimation mechanisms in humans that may underlie optimal decision making.     

Neuronal decision-making circuits

Studying the neural basis of decision-making has largely taken one of two paths: one has involved cell-by-cell characterization of neuronal circuits in invertebrates; and the other, single-unit studies of monkeys performing cognitive tasks. Here I shall attempt to bring these two disparate approaches together.     

Composite collective decision-making

Individual animals are adept at making decisions and have cognitive abilities, such as memory, which allow them to hone their decisions. Social animals can also share information. This allows social animals to make adaptive group-level decisions. Both individual and collective decision-making systems also have drawbacks and limitations, and while both are well studied, the interaction between them is still poorly understood. Here, we study how individual and collective decision-making interact during ant foraging. We first gathered empirical data on memory-based foraging persistence in the ant Lasius niger. We used these data to create an agent-based model where ants may use social information (trail pheromones), private information (memories) or both to make foraging decisions. The combined use of social and private information by individuals results in greater efficiency at the group level than when either information source was used alone. The modelled ants couple consensus decision-making, allowing them to quickly exploit high-quality food sources, and combined decision-making, allowing different individuals to specialize in exploiting different resource patches. Such a composite collective decision-making system reaps the benefits of both its constituent parts. Exploiting such insights into composite collective decision-making may lead to improved decision-making algorithms.     

Artificial neural networks for decision-making in urologic oncology

Artificial neural networks (ANNs) are computational methodologies that perform multifactorial analyses, inspired by networks of biological neurons. Like neural networks, ANNs contain layers of simple points (nodes) of data that interract through carefully weighted connection lines. ANNs are "trained" and balanced by having been previously fed data, which the ANN uses as the means for adjusting its interconnections. Studies have shown that novel and highly accurate ANNs significantly enhance the ability to detect prostate cancer early (high sensitivity) while avoiding a greater number of unnecessary tissue samplings (high specificity). The use of ANNs in prostate cancer is ideal because of 1) multiple predicting factors that influence outcome; 2) the desire to offer individual consulting based on various tests; 3) the fact that prior logistic regression analysis results have had serious limitations in application; and 4) the need for an up-to-date tool that can apply easily to everyone. An ANN should be seen as an important tool that is complementary to the physician's personal knowledge and judgment in making decisions.