Evolution and gradualness

Evolutionary systems are commonly considered to have two fundamental properties: (1) elements (or organisms) in the system reproduce with mutation and (2) only the fit elements survive. I propose that evolutionary systems have a third property — the property of gradualness. A system has gradualness, if, and only if, small changes in an element usually lead to small changes in that element's fitness.I have formalized a framework from which attempts to design evolutionary systems might proceed. Of particular importance are the criteria, based on the notion of perpetuation, which a system's behavior must satisfy in order to be considered evolutionary. By my standards, no computer programs have been designed that manifest meaningful evolutionary behavior.     

Searching genomes for ribozymes and riboswitches

New regulatory RNAs with complex structures have recently been discovered, among them the first catalytic riboswitch, a gene-regulatory RNA sequence with catalytic activity. Here we discuss some of the experimental approaches and theoretical difficulties attached to the identification of new ribozymes in genomes.     

Searching for schizophrenia genes

Schizophrenia is characterized by profound disturbances of cognition, emotion and social functioning. It carries a lifetime risk within the general population of approximately 1%. Genetic epidemiological studies have shown that the syndrome has a high heritability, indicating a significant genetic component to its aetiology. However, the undoubted complexity and probable heterogeneity of the disorder continue to confound research, and the precise underlying neurobiological mechanisms remain largely unknown. Although molecular-genetic approaches face formidable difficulties, the identification of susceptibility genes is likely to provide valuable insights into the aetiology and pathogenesis that could lead to the development of more effective treatments.     

寻找洞穴鱼

2004年12月,《人与生物圈》杂志记者、摄影师等一行三人到茂兰保护区考察。听说这里有一种非常珍稀而神秘的洞穴盲鱼——荔波盲条鳅,他们为之一振,希望能一睹荔波盲条鳅的倩影,同时也希望茂兰保护区能把这一珍稀鱼类的物种现状搞清楚,弄清这一物种究竟还存不存在,如还存在,应如何采取相应措施加强保护。管理局随即决定由我和另几位同事及摄影师组成一个精干的考察小分队,     

Searching for nuclear-mitochondrial genes

Recently, a novel strategy has been developed to identify yeast genes that are important for mitochondrial respiratory chain function. This approach found a large number of genes that were not previously thought to be involved, providing new candidate disease genes for mitochondrial disorders. These genes could cast light on the intricate relationship between genotype and phenotype in a wide range of inherited human diseases.     

Searching the protein sequence database

As the volume of protein sequence data grows, rapid methods for searching the protein sequence database become of primary importance. Rigorous comparison of sequences is obtained with the well-known dynamic programming algorithms. However, these algorithms are not rapid enough to use for routinely searching the entire database. In this paper we discuss some methods that can be used for rapid searches.     

Searching the Clinical Fitness Landscape

Widespread unexplained variations in clinical practices and patient outcomes suggest major opportunities for improving the quality and safety of medical care. However, there is little consensus regarding how to best identify and disseminate healthcare improvements and a dearth of theory to guide the debate. Many consider multicenter randomized controlled trials to be the gold standard of evidence-based medicine, although results are often inconclusive or may not be generally applicable due to differences in the contexts within which care is provided. Increasingly, others advocate the use “quality improvement collaboratives”, in which multi-institutional teams share information to identify potentially better practices that are subsequently evaluated in the local contexts of specific institutions, but there is concern that such collaborative learning approaches lack the statistical rigor of randomized trials. Using an agent-based model, we show how and why a collaborative learning approach almost invariably leads to greater improvements in expected patient outcomes than more traditional approaches in searching simulated clinical fitness landscapes. This is due to a combination of greater statistical power and more context-dependent evaluation of treatments, especially in complex terrains where some combinations of practices may interact in affecting outcomes. The results of our simulations are consistent with observed limitations of randomized controlled trials and provide important insights into probable reasons for effectiveness of quality improvement collaboratives in the complex socio-technical environments of healthcare institutions. Our approach illustrates how modeling the evolution of medical practice as search on a clinical fitness landscape can aid in identifying and understanding strategies for improving the quality and safety of medical care.