Development and validation of biomarker classifiers for treatment selection

Many syndromes traditionally viewed as individual diseases are heterogeneous in molecular pathogenesis and treatment responsiveness. This often leads to the conduct of large clinical trials to identify small average treatment benefits for heterogeneous groups of patients. Drugs that demonstrate effectiveness in such trials may subsequently be used broadly, resulting in ineffective treatment of many patients. New genomic and proteomic technologies provide powerful tools for the selection of patients likely to benefit from a therapeutic without unacceptable adverse events. In spite of the large literature on developing predictive biomarkers, there is considerable confusion about the development and validation of biomarker-based diagnostic classifiers for treatment selection. In this paper we attempt to clarify some of these issues and to provide guidance on the design of clinical trials for evaluating the clinical utility and robustness of pharmacogenomic classifiers.     

Clustering objects on subsets of attributes (with discussion)

Summary.  A new procedure is proposed for clustering attribute value data. When used in conjunction with conventional distance-based clustering algorithms this procedure encourages those algorithms to detect automatically subgroups of objects that preferentially cluster on subsets of the attribute variables rather than on all of them simultaneously. The relevant attribute subsets for each individual cluster can be different and partially (or completely) overlap with those of other clusters. Enhancements for increasing sensitivity for detecting especially low cardinality groups clustering on a small subset of variables are discussed. Applications in different domains, including gene expression arrays, are presented.     

回族起源的DNA证据

应用现代DNA分析技术,研究回族的起源、迁徙、融合、演变,探讨回族与其他民族之间的关系及有关发展规律,应是回族学研究的一个值得重视的方面。本文利用本实验室积累,综合国内外其他族群基因资料,以群体角度从DNA水平探讨了回族的起源、迁徙、演化等问题,证实了以往大多数人类学调查的结果,即回族与北方民族之间有相当大的融合。并且明确了回族中有较大比例的高加索人种的混杂程度,而这种基因流动应该主要与唐宋时期西域商贾、使者留居和蒙元时期蒙古人西征有密切关系,为传统的回族学研究提供了新视角。     

The unconscious in economic decision-making: Convergent voices

Mainstream economics assumes that decision-making is a conscious cost-benefit process, ignoring the pervasive role of unconscious thought processes. Recent research in neuroimaging, genomics, and psychoanalysis exposes the role of unconscious and “nonconscious” processes, providing tools for analyzing economic decision-making. Neuroimaging reveals examples of brain function that modulate decision-making, but are not under conscious control. Psychoanalytic research provides evidence of the role of emotions and the unconscious in human behavior and decision-making. We advance the case for integrating psychoanalysis and neuroscience for a new perspective on the role of the mind in decision-making and economic behavior.     

Observational studies,clinical trials,and the women’s health initiative

The complementary roles fulfilled by observational studies and randomized controlled trials in the population science research agenda is illustrated using results from the Women’s Health Initiative (WHI). Comparative and joint analyses of clinical trial and observational study data can enhance observational study design and analysis choices, and can augment randomized trial implications. These concepts are described in the context of findings from the WHI randomized trials of postmenopausal hormone therapy and of a low-fat dietary pattern, especially in relation to coronary heart disease, stroke, and breast cancer. The role of biomarkers of exposure and outcome, including high-dimensional genomic and proteomic biomarkers, in the elucidation of disease associations, will also be discussed in these same contexts.