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Biology subjects

Forger, D.

Publications and source records attributed to Forger, D..

3 recordsLinked to original sources

Whole-cortex simulation reveals spatiotemporal patterns emerging from the interplay of network connectivity and intracellular dynamics

Recent advances in Graphics Processing Unit (GPU) computing have allowed for computational models of whole-brain activity at unprecedented scales. In this work, we use desktop computers to build and simulate a whole-cortex mouse brain model using Hodgkin-Huxley type models for all the most active neurons in the mouse cortex. We compare the model dynamics over different types of connectivity, ranging from uniform random to realistic connectivity derived from experimental data on cell positions and the Allen Brain Atlas. By changing the external drive and coupling strength of neurons in the network, we can produce a wide range of oscillations in the gamma through delta bands. While the global mean-field behaviors of different connectivities share some similarities, an experimentally determined hierarchical connectivity allows for complex, heterogeneous behaviors typically seen in EEG recordings that are not observed in networks with nearest neighbors or uniform coupling. Moreover, our simulations reveal a wide range of spatiotemporal patterns, such as rotational or planar traveling waves, that are observed in experiments. Different traveling waves are observed with different connectivity and coupling strengths on the same connectivity. Our simulations show that many cortical behaviors emerge at scale with the full complexity of the network structure and ionic dynamics. We also provide a computational framework to explore these cortex- wide behaviors further.

neuroscience↗

Inferring causality in biological oscillators

A fundamental goal of biological study is to identify regulatory interactions among components. The recent surge in time-series data collection in biology provides a unique opportunity to infer regulatory networks computationally. However, when the components oscillate, model-free inference methods, while easily implemented, struggle to distinguish periodic synchrony and causality. Alternatively, model-based methods test whether time series are reproducible with a specific model but require inefficient simulations and have limited applicability. Here, we develop an inference method based on a general model of molecular, neuronal, and ecological oscillatory systems that merges the advantages of both model-based and model-free methods, namely accuracy, broad applicability, and usability. Our method successfully infers the positive and negative regulations of various oscillatory networks, including the repressilator and a network of cofactors of pS2 promoter, outperforming popular inference methods. We also provide a computational package, ION (Inferring Oscillatory Networks), that users can easily apply to noisy, oscillatory time series to decipher the mechanisms by which diverse systems generate oscillations.

systems biology↗

Gene-Set Enrichment with Mathematical Biology (GEMB)

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 the differential contributions of each gene. Extending this concept further, mathematical models of biology can be leveraged to define gene interactions based on biophysical principles by predicting the effects of genetic perturbations on a particular downstream function. 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. Using publicly-available summary data from the Psychiatric Genetics Consortium (n=41,653; ~9) million SNPs), we examine an a priori hypothesis that intracellular calcium ion concentrations contribute to bipolar disorder. In this case study, we are able to strengthen inferences from a P-value of 0.081 to 1.7x10-4 by moving from a general calcium signaling pathway to a specific model-predicted function.

genetics↗