The Computational Diet: A Review of Computational Methods Across Diet, Microbiome, and Health.

Food and human health are inextricably linked. As such, revolutionary impacts on health have been derived from advances in the production and distribution of food relating to food safety and fortification with micronutrients. During the past two decades, it has become apparent that the human microbiome has the potential to modulate health, including in ways that may be related to diet and the composition of specific foods. Despite the excitement and potential surrounding this area, the complexity of the gut microbiome, the chemical composition of food, and their interplay in situ remains a daunting task to fully understand. However, recent advances in high-throughput sequencing, metabolomics profiling, compositional analysis of food, and the emergence of electronic health records provide new sources of data that can contribute to addressing this challenge. Computational science will play an essential role in this effort as it will provide the foundation to integrate these data layers and derive insights capable of revealing and understanding the complex interactions between diet, gut microbiome, and health. Here, we review the current knowledge on diet-health-gut microbiota, relevant data sources, bioinformatics tools, machine learning capabilities, as well as the intellectual property and legislative regulatory landscape. We provide guidance on employing machine learning and data analytics, identify gaps in current methods, and describe new scenarios to be unlocked in the next few years in the context of current knowledge

NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets

Allele-specific length preference for 24 MHC molecules characterized by 20 or more ligand data points for the allmer and 9mer prediction methods compared to the length preference in the SYFPEITHI data. Length profiles for the allmer and 9mer methods were estimated as described in the text. (XLSX 50 kb

Catching the Video Virus

In the process of computer-mediated exchange, some online videos travel from one person to another resulting in the process of diffusion of the video. However, there are very few empirical investigations of the audience involved in the process. This exploratory research employs Rogers\u27 diffusion of innovations as a theoretical framework to study online video users. Theories from social networks on tie strength and homophily are applied to create an integrated diffusion model. Based on survey data from college students, online video audience was profiled in two ways: one based on individual characteristics and another on activities with video content. Participants in the viral transmission process were found to be novelty-seekers, highly connected to others and appreciative of entertaining videos. An integrated model exploring the antecedents of viral transmission of online videos identified age, sex, Internet usage, and network connectedness as significant predictors. Contrary to previous findings, strong and homophilous ties were found to significantly contribute toward the viral spread. The findings of this study will add to the body of knowledge on diffusion research by enhancing understanding of individuals involved in an evolving medium. A profile of online video users will help marketers identify and reach the right audienc

Social Media in Baptist Churches

The integration of social media into Chicago Baptist Churches congregants recently increased over the last few years. This research study allowed church leaders to determine if social media was an effective media outlet in Baptist churches on the Southside of Chicago. The evaluation research approach was to assess the effectiveness of social media, in particular Facebook and Instagram. Within this conceptual framework, the researcher was able to produced flexible, fixed, and multi-design strategies to abstract a full spectrum of evaluation. The subsequent methodology focused on the dual use of social media and themes that coincide, specifically, marketing, politics, communication awareness, engagement behaviors, viral advertising, and engagement. Twenty-five participants responded to the 21 questions on the Baptist Leadership and Social Media Survey. Results showed that there was a strong, positive, and statistically significant correlation in daily use between the two types of media. For Facebook, the differences showed a strong statistical trend and there was a very strong effect of age. For Instagram, the differences were significant and there was again a very strong effect of age. With respect to changing their current use of social media in the future, men were very likely to change their use of Facebook in the future whereas on women were somewhat to very likely to; however, the difference was non-significant, and the gender effect was small. Men were ‘not so likely’ to change their current use of Instagram whereas women were not at all to not so likely to change in the future; however, this difference was also non-significant, and the gender effect was small

Investigations of the DNA-binding activity and gene regulatory properties of IRF3, IRF5, and IRF7 homodimers

The innate immune response is an essential component of the mammalian immune system that responds rapidly to pathogens. This response to pathogens is initiated by the detection of pathogen associated molecular patterns (PAMPs) by pathogen recognition receptors (PRRs). PRR signaling activates antipathogen gene programs via transcription factors (TFs) such as the interferon regulatory factors (IRFs). IRF3, IRF5, and IRF7 (IRF3/5/7) are key signal-dependent TFs that have overlapping, yet distinct, roles in the mammalian response to pathogens. To examine the role that DNA-binding specificity plays in delineating IRF3/5/7-specific gene regulation, we used protein-binding microarrays (PBMs) to characterize the DNA binding of IRF3/5/7 homodimers. We identified both common and dimer-specific DNA binding sites, and show that DNA-binding differences can translate into dimer-specific gene regulation. Central to the antiviral response, IRF3/5/7 regulate type I interferon (IFN) genes. We show that IRF3 and IRF7 bind to many interferon-stimulated response element (ISRE)-type sites in the virus-response elements (VREs) of IFN promoters. However, strikingly, IRF5 does not bind the VREs, suggesting evolutionary selection against IRF5 homodimer binding. Mutational analysis identified a a critical specificity-determining residue that inhibits IRF5 binding to the ISRE-variants present in the IFN gene promoters. Integrating PBM and reporter gene data we find that both DNA-binding affinity and affinity-independent mechanisms determine the transcriptional activation ability of DNA-bound IRF dimers, suggesting that DNA-based allostery plays a role in IRF binding site function. To assay the sequence determinants of IRF-dependent transcriptional regulation, we propose using a modified massively parallel reporter assay (MPRA). The proposed MPRA leverages unique molecular identifiers to improve the accuracy of reporter gene quantitation. This work provides new insights into the role and limitations of DNA-binding affinity in delineating IRF3/5/7-specific gene expression and lays groundwork for further understanding the complexities of IRF-dependent transcriptional regulation of innate immune genes

Genome-wide analysis of mobile genetic element insertion sites

Mobile genetic elements (MGEs) account for a significant fraction of eukaryotic genomes and are implicated in altered gene expression and disease. We present an efficient computational protocol for MGE insertion site analysis. ELAN, the suite of tools described here uses standard techniques to identify different MGEs and their distribution on the genome. One component, DNASCANNER analyses known insertion sites of MGEs for the presence of signals that are based on a combination of local physical and chemical properties. ISF (insertion site finder) is a machine-learning tool that incorporates information derived from DNASCANNER. ISF permits classification of a given DNA sequence as a potential insertion site or not, using a support vector machine. We have studied the genomes of Homo sapiens, Mus musculus, Drosophila melanogaster and Entamoeba histolytica via a protocol whereby DNASCANNER is used to identify a common set of statistically important signals flanking the insertion sites in the various genomes. These are used in ISF for insertion site prediction, and the current accuracy of the tool is over 65%. We find similar signals at gene boundaries and splice sites. Together, these data are suggestive of a common insertion mechanism that operates in a variety of eukaryotes

Measuring transcription factor binding and gene expression using barcoded self-reporting transposon calling cards and transcriptomes

Calling cards technology using self-reporting transposons enables the identification of DNA-protein interactions through RNA sequencing. Although immensely powerful, current implementations of calling cards in bulk experiments on populations of cells are technically cumbersome and require many replicates to identify independent insertions into the same genomic locus. Here, we have drastically reduced the cost and labor requirements of calling card experiments in bulk populations of cells by introducing a DNA barcode into the calling card itself. An additional barcode incorporated during reverse transcription enables simultaneous transcriptome measurement in a facile and affordable protocol. We demonstrate that barcoded self-reporting transposons recove

Optogenetic interrogation of primary visual cortex and its impact on neural coding and behavior

Understanding the mechanism by which the brain transforms simple sensory inputs into rich perceptual experiences is one of the great mysteries of systems neuroscience. Undoubtedly this involves the activity of large populations of interconnected neurons, but while the responses of individual neurons to a variety of sensory stimuli have been well-characterized, how populations of such neurons organize their activity to create our sensory perceptions is almost entirely unknown. To investigate this complex circuitry requires the ability to causally manipulate the activity of neural populations and monitor the resultant effects. Here we focus on primary visual cortex (V1), which has been shown to be crucial for visual perception, and utilize optogenetic tools to render the activity of genetically- defined neural populations sensitive to light. By simultaneously recording and modulating (either driving or silencing) the activity of excitatory (glutamatergic) neurons, we are able to causally examine their role in visual perception. Here we report 3 major findings. First, we show that activating subpopulations of excitatory neurons can improve visual perception under certain conditions and that information in V1 used for perceptual decisions is integrated across spatially-limited populations of neurons. Further, we show that a key signature of this information integration is a reduction in correlated variability between neurons. Correlated variability has been implicated as a major source of behavioral choice related activity in the cortex, and theorized to be a major factor limiting information in cortical populations. However, until now, there has not been a way to manipulate correlations without altering firing rates or other task related variables. Here we demonstrate a novel method using optogenetic stimulation to causally manipulate correlated variability between cortical neurons without altering their firing rates. Lastly, with the goal of expanding the currently limited repertoire of optogenetic tools for non-human primates, we establish the viability of a novel optogenetic construct capable of dramatically silencing neural populations using a recently discovered anion conducting channelrhodopsin