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Background Gene-set analyses measure the association between a disease of interest and a "set" of genes related to a biological pathway. These analyses often incorporate gene network properties to account for differential contributions of each gene. We extend this concept further—defining gene contributions based on biophysical properties—by leveraging mathematical models of biology to predict the effects of genetic perturbations on a particular downstream function. Results We present a method that combines gene weights from model predictions and gene ranks from genome-wide association studies into a weighted gene-set test. We demonstrate in simulation how such a method can improve statistical power. To this effect, we identify a gene set, weighted by model-predicted contributions to intracellular calcium ion concentration, that is significantly related to bipolar disorder in a small dataset (P = 0.04; n = 544). We reproduce this finding using publicly available summary data from the Psychiatric Genomics Consortium (P = 1.7 × 10−4; n = 41,653). By contrast, an approach using a general calcium signaling pathway did not detect a significant association with bipolar disorder (P = 0.08). The weighted gene-set approach based on intracellular calcium ion concentration did not detect a significant relationship with schizophrenia (P = 0.09; n = 65,967) or major depression disorder (P = 0.30; n = 500,199). Conclusions Together, these findings show how incorporating math biology into gene-set analyses might help to identify biological functions that underlie certain polygenic disorders. [ABSTRACT FROM AUTHOR]

Complex life cycles involve a set of discrete stages that can differ dramatically in form and function. Transitions between different stages vary in nature and magnitude; likewise, the degree of autonomy among stages enabled by these transitions can vary as well. Because the selective value of traits is likely to shift over ontogeny, the degree of autonomy among stages is important for understanding how processes at one life-history stage alter the conditions for performance and selection at others. We pose 3 questions that help to define a research focus on processes that integrate function across life cycles. First, to what extent do particular transitions between life-history stages allow those stages to function as autonomous units? We identify the roles that stages play in the life history, types of transitions between stages, and 3 forces (structural, genetic/ epigenetic, and experiential) that can contribute to integration among stages. Second, what are the potential implications of integration across life cycles for assumptions and predictions of life-history theory? We provide 3 examples where theory has traditionally focused on processes acting within stages in isolation from others. Third, what are the long-term consequences of carryover of experience from one life cycle stage to the next? We distinguish 3 scenarios: persistence (effects of prior experience persist through subsequent stages), amplification (effects persist and are magnified at subsequent stages), and compensation (effects are compensated for and diminish at subsequent stages). We use these scenarios to differentiate between effects of a carryover of state and carryover into subsequent processes. The symposium introduced by our discussion is meant to highlight how discrete stages can be functionally coupled, such that life cycle evolution becomes a more highly integrated response to selection than can be deduced from the study of individual stages. [ABSTRACT FROM AUTHOR]

Brazilian free-tailed bats (Tadarida brasiliensis) are one of the most widely distributed bat species in the Americas, often engaging in rapid, long-distance dispersals. Here, we document that, since ca. 2007, these bats have expanded their range into western North Carolina, eastern Tennessee and Virginia. Reports from wildlife control professionals, wildlife rehabilitators, regional submissions of bats for rabies testing, acoustic monitoring and the presence of T. brasiliensis in buildings and bat houses indicate that these bats are now established in year-round colonies in areas previously thought outside their range limits. The geographic distributions of many organisms are currently shifting to higher latitudes in response to changing climate. We hypothesize that a coldtolerant thermal physiology that allows these largely tropical bats to enter extended torpor contributes to the ability of T. brasiliensis to establish populations in formerly cooler regions and propose that their rapid northward expansion is facilitated by climate change and their tendency to explore new habitats and use a wide diversity of roost sites. Because of their abundance and use of man-made structures, we anticipate that the range expansion of T. brasiliensis will have implications for public health, ecosystem services and bat conservation. [ABSTRACT FROM AUTHOR]