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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Intact extrastriate visual network without primary visual cortex in a Rhesus macaque with naturally occurring Blindsight

Lesions of primate primary visual cortex (V1) lead to loss of conscious visual perception, and are often devastating to those affected. Understanding the neural consequences of such damage may aid the development of rehabilitation methods. In this rare case of a Rhesus macaque (monkey S), likely born without V1, we investigated the brain structures underlying residual visual abilities using multimodal magnetic resonance imaging. In-group behaviour was unremarkable. Compared to controls, visual structures outside of monkey Ss lesion appeared normal. Visual stimulation under anaesthesia with checkerboards activated lateral geniculate nucleus of monkey S, but not the pulvinar, while full-field moving dots activated the pulvinar. Functional connectivity analysis revealed a network of bilateral dorsal visual areas temporally correlated with V5/MT, consistent across lesion and control animals. Overall, we found an intact network of visual cortical areas even without V1, but little evidence for strengthened subcortical input to V5/MT supporting residual visual function.

neuroscience↗

bioRxiv2018

Tactile enrichment drives emergence of functional columns and improves sensory coding in L2/3 of mouse S1

Sensory maps in layer (L) 2/3 of rodent cortex lack precise functional column boundaries, and instead exhibit locally heterogeneous tuning superimposed on smooth global topography. Could this organization be a byproduct of impoverished experience in laboratory housing? We compared whisker map somatotopy in L2/3 and L4 excitatory cells of somatosensory (S1) cortex in normally housed vs. tactile-enriched mice, using GCaMP6s imaging. Normally housed mice had a dispersed, salt-and-pepper whisker map in L2/3, but L4 was more topographically precise. Enrichment (P21 to P46-71) sharpened whisker tuning and decreased, but did not abolish, local tuning heterogeneity. In L2/3, enrichment strengthened and sharpened whisker point representations, and created functional boundaries of tuning similarity and noise correlations at column edges. Thus, tactile experience drives emergence of functional columnar topography in S1, and reduces salt-and-pepper tuning heterogeneity. These changes predict improved single-trial population coding of whisker deflections within each column.

neuroscience↗

bioRxiv2018

Geometrical structure of perceptual color space: mental representations and adaptation invariance

A central issue in neuroscience is to understand how the brain builds structured representations of percepts that facilitate useful inferences about the world. Similarity between percepts is used to accomplish many everyday tasks, e.g. object identification, so is widely used to construct geometrical spaces that represent stimulus qualities, but the intrinsic validity of the geometry is not tested critically. We introduce an experimental approach to equating relative similarities by setting perceived midpoints between pairs of stimuli. Midpoint settings are used with Varignons Theorem to test the intrinsic geometry of a representation space, and its mapping to a physical space of stimuli. For perceptual color space, we demonstrate that geometrical structure depends on the mental representation used in judging similarity: an affine geometry is valid only when observers use an opponent-color mental representation. An affine geometry implies that similarity can be judged within straight lines and across parallel lines, and its neural coding could involve ratios of responses. We show that this perceptual space is invariant to changes in illumination color, providing a formal justification to generalize to all of color space, color constancy results measured for color categories. Our midpoint measurements deviate significantly from midpoints in the \"uniform\" color spaces CIELAB and CIELUV, used extensively in industry and research, so these spaces do not provide adequate metric representation of perceived colors. Our paradigm can thus test for intrinsic geometrical assumptions underlying the representation space for many perceptual modalities, and for the extrinsic perceptual geometry of the space of physical stimuli.\n\nSignificanceMathematical spaces based on similarity judgments are widely used to represent stimulus qualities in perception, cognition and neuroscience. We introduce a perceptual approach to equate relative similarities, and use them to test the geometry of a perceptual space and its mapping to a physical space of stimuli. For color perception, our results show that perceptual geometry depends on the mental representation used in judging similarity, and it has an affine structure when observers use an opponent-color representation. An affine geometry implies that neural coding of similarity could involve simple ratios of responses. Our measurements also reveal that the uniform color spaces CIELAB and CIELUV, used extensively in industrial applications, do not provide adequate representation of similarity between moderately spaced colors.

neuroscience↗

bioRxiv2018

Targeted memory reactivation during sleep to strengthen memory for arbitrary pairings

A powerful way to investigate memory consolidation during sleep utilizes acoustic stimulation to reactivate memories. In multiple studies, Targeted Memory Reactivation (TMR) using sounds associated with prior learning improved later memory, as in recalling locations where objects previously appeared. In the present experiment, we examined whether a variant of the same technique could strengthen memory for the locations of pairs of objects. Each sound was naturally connected to one object from each pair, but we hypothesized that both memories could be improved with TMR. We first asked participants to memorize each of 50 pairs of objects by associating the two objects with each other and with the sound of one of the objects (e.g., cat-meow). Next, objects were presented in unique locations on a grid. Participants learned these locations in an adaptive procedure. During an afternoon nap, 25 of the sounds were quietly presented. In memory tests given twice before and twice after the nap, participants heard the sound for each object pair and were asked to recall the name of the second object and the locations of both objects. Forgetting scores were calculated using the mean difference between pre-nap and post-nap spatial recall errors. We found less forgetting after the nap for cued compared to non-cued objects. Additionally, the extent of forgetting tended to be similar for the two members of each pair, but only for cued pairs. Results thus substantiate the potential for sounds to reactivate spatial memories during sleep and thereby improve subsequent recall performance, even for multiple objects associated with a single sound and when participants must learn a novel sound-object association.\n\nHighlightsO_LIMemories can be improved during sleep using arbitrary sounds\nC_LIO_LIParticipants learned a random screen location for each of 100 objects\nC_LIO_LIObjects were learned in pairs with the characteristic sound of one of the objects\nC_LIO_LIHalf of those sounds were presented during a nap that followed learning\nC_LIO_LIAfter sleep, location recall was more accurate for cued than for non-cued objects\nC_LI

neuroscience↗

bioRxiv2018

Naked mole rat hyaluronan - an extreme folding biopolymer

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring-like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking contrasting. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.

biophysics↗

bioRxiv2018

Mutation detection in thousands of acute myeloid leukemia cells using single cell RNA-sequencing

Virtually all tumors are genetically heterogeneous, containing subclonal populations of cells that are defined by distinct mutations1. Subclones can have unique phenotypes that influence disease progression2, but these phenotypes are difficult to characterize: subclones usually cannot be physically purified, and bulk gene expression measurements obscure interclonal differences. Single-cell RNA-sequencing has revealed transcriptional heterogeneity within a variety of tumor types, but it is unclear how this expression heterogeneity relates to subclonal genetic events - for example, whether particular expression clusters correspond to mutationally defined subclones3,4,5,6-9. To address this question, we developed an approach that integrates enhanced whole genome sequencing (eWGS) with the 10x Genomics Chromium Single Cell 5 Gene Expression workflow (scRNA-seq) to directly link expressed mutations with transcriptional profiles at single cell resolution. Using bone marrow samples from five cases of primary human Acute Myeloid Leukemia (AML), we generated WGS and scRNA-seq data for each case. Duplicate single cell libraries representing a median of 20,474 cells per case were generated from the bone marrow of each patient. Although the libraries were 5 biased, we detected expressed mutations in cDNAs at distances up to 10 kbp from the 5 ends of well-expressed genes, allowing us to identify hundreds to thousands of cells with AML-specific somatic mutations in every case. This data made it possible to distinguish AML cells (including normal-karyotype AML cells) from surrounding normal cells, to study tumor differentiation and intratumoral expression heterogeneity, to identify expression signatures associated with subclonal mutations, and to find cell surface markers that could be used to purify subclones for further study. The data also revealed transcriptional heterogeneity that occurred independently of subclonal mutations, suggesting that additional factors drive epigenetic heterogeneity. This integrative approach for connecting genotype to phenotype in AML cells is broadly applicable for analysis of any sample that is phenotypically and genetically heterogeneous.

cancer biology↗

bioRxiv2018

Variably methylated regions in the newborn epigenome: environmental, genetic and combined influences

BackgroundEpigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. We examined the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs), defined as consecutive CpGs showing the highest variability of DNAm in 4 independent cohorts (PREDO, DCHS, UCI, MoBa, N=2,934).\n\nResultsWe used Akaikes information criterion to test which factors best explained variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E) including maternal demographic, psychosocial and metabolism related phenotypes, genotypes in cis (G), or their additive (G+E) or interaction (GxE) effects. G+E and GxE models consistently best explained variability in DNAm of VMRs across the cohorts, with G explaining the remaining sites best. VMRs best explained by G, GxE or G+E, as well as their associated functional genetic variants (predicted using deep learning algorithms), were located in distinct genomic regions, with different enrichments for transcription and enhancer marks. Genetic variants of not only G and G+E models, but also of variants in GxE models were significantly enriched in genome wide association studies (GWAS) for complex disorders.\n\nConclusionGenetic and environmental factors in combination best explain DNAm at VMRs. The CpGs best explained by G, G+E or GxE are functionally distinct. The enrichment of GxE variants in GWAS for complex disorders supports their importance for disease risk.

genetics↗

bioRxiv2018

The biggest losers: Habitat isolation deconstructs complex food webs from top to bottom

Habitat fragmentation is threatening global biodiversity. To date, there is only limited understanding of how habitat fragmentation or any alteration to the spatial structure of a landscape in general, affects species diversity within complex ecological networks such as food webs. Here, we present a dynamic and spatially-explicit food web model which integrates complex food web dynamics at the local scale and species-specific dispersal dynamics at the landscape scale, allowing us to study the interplay of local and spatial processes in metacommunities. We explore how habitat fragmentation, defined as a decrease of habitat availability and an increase of habitat isolation, affects the species diversity patterns of complex food webs (-, {beta}-,{gamma} -diversity), and specifically test whether there is a trophic dependency in the effect of habitat fragmentation on species diversity. In our model, habitat isolation is the main driver causing species loss and diversity decline. Our results emphasise that large-bodied consumer species at high trophic positions go extinct faster than smaller species at lower trophic levels, despite being superior dispersers that connect fragmented landscapes better. We attribute the loss of top species to a combined effect of higher biomass loss during dispersal with increasing habitat isolation in general, and the associated energy limitation in highly fragmented landscapes, preventing higher trophic levels to persist. To maintain trophic-complex and species-rich communities calls for effective conservation planning which considers the interdependence of trophic and spatial dynamics as well as the spatial context of a landscape and its energy availability.

ecology↗

bioRxiv2018

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individuals own genotype on BW and subsequent disease risk from indirect effects of their mothers correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offsprings later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

genetics↗

bioRxiv2018

The genome-wide, multi-layered architecture of chromosome pairing in early Drosophila embryos

Genome organization involves cis and trans chromosomal interactions, both implicated in gene regulation, development, and disease. Here, we focused on trans interactions in Drosophila, where homologous chromosomes are paired in somatic cells from embryogenesis through adulthood. We first addressed the long-standing question of whether pairing extends genome-wide and, to this end, developed a haplotype-resolved Hi-C approach that uses a new strategy to minimize homolog misassignment and thus robustly distinguish trans-homolog from cis contacts. This approach revealed striking genome-wide pairing in Drosophila embryos. Moreover, we discovered pairing to be surprisingly structured, with trans-homolog domains and interaction peaks, many coinciding with the positions of analogous cis features. We also found a significant correlation between pairing and the chromatin accessibility mediated by the pioneer factor Zelda. Our findings reveal a complex, highly structured organization underlying homolog pairing, first discovered more than a century ago.\n\nOne Sentence SummaryA robust approach for haplotype-resolved Hi-C reveals highly-structured homolog pairing in early stage Drosophila embryos.

genetics↗

bioRxiv2018

The History, Advocacy and Efficacy of Data Management Plans

Data management plans (DMPs) have increasingly been encouraged as a key component of institutional and funding body policy. Although DMPs necessarily place administrative burden on researchers, proponents claim that DMPs have myriad benefits, including enhanced research data quality, increased rates of data sharing, and institutional planning and compliance benefits.\n\nIn this manuscript, we explore the international history of DMPs and describe institutional and funding body DMP policy. We find that economic and societal benefits from presumed increased rates of data sharing was the original driver of mandating DMPs by funding bodies. Today, 86% of UK Research Councils and 63% of US funding bodies require submission of a DMP with funding applications. Given that no major Australian funding bodies require DMP submission, it is of note that 37% of Australian universities have taken the initiative to internally mandate DMPs.\n\nInstitutions both within Australia and internationally frequently promote the professional benefits of DMP use, and endorse DMPs as best practice. We analyse one such typical DMP implementation at a major Australian institution, finding that DMPs have low levels of apparent translational value. Indeed, an extensive literature review suggests there is very limited published systematic evidence that DMP use has any tangible benefit for researchers, institutions or funding bodies.\n\nWe are therefore led to question why DMPs have become the go-to tool for research data professionals and advocates of good data practice. By delineating multiple use-cases and highlighting the need for DMPs to be fit for intended purpose, we question the view that a good DMP is necessarily that which encompasses the entire data lifecycle of a project. Finally, we summarise recent developments in the DMP landscape, and note a positive shift towards evidence-based research management through more researcher-centric, educative, and integrated DMP services.

scientific communication and education↗

bioRxiv2018

Highly Structured Homolog Pairing Reflects Functional Organization of the Drosophila Genome

Trans-homolog interactions encompass potent regulatory functions, which have been studied extensively in Drosophila, where homologs are paired in somatic cells and pairing-dependent gene regulation, or transvection, is well-documented. Nevertheless, the structure of pairing and whether its functional impact is genome-wide have eluded analysis. Accordingly, we generated a diploid cell line from divergent parents and applied haplotype-resolved Hi-C, discovering that homologs pair relatively precisely genome-wide in addition to establishing trans-homolog domains and compartments. We also elucidated the structure of pairing with unprecedented detail, documenting significant variation across the genome. In particular, we characterized two forms: tight pairing, consisting of contiguous small domains, and loose pairing, consisting of single larger domains. Strikingly, active genomic regions (A-type compartments, active chromatin, expressed genes) correlated with tight pairing, suggesting that pairing has a functional role genome-wide. Finally, using RNAi and haplotype-resolved Hi-C, we show that disruption of pairing-promoting factors results in global changes in pairing.\n\nOne Sentence SummaryHaplotype-resolved Hi-C reveals structures of homolog pairing and global implications for gene activity in hybrid PnM cells.

genetics↗

bioRxiv2018

A redox-regulated type III metacaspase controls cell death in a marine diatom

Programmed cell death (PCD) in marine phytoplankton was suggested as one of the mechanisms that facilitates large scale bloom demise. Yet, the molecular basis for algal PCD machinery is rudimentary. Metacaspases are considered ancestral proteases that regulate cell death, but their activity and role in algae are still elusive. Here we biochemically characterized a recombinant metacaspase 5 from the model diatom Phaeodactylum tricornutum (PtMC5), revealing calcium-dependent protease activity. This activity includes auto-processing and cleavage following arginine. PtMC5 overexpressing cells exhibited higher metacaspase activity and were more sensitive to a diatom-specific infochemical compared to WT cells. Mutagenesis of potential disulfide-forming cysteines decreased PtMC5 activity, suggesting redox regulation. This cysteine pair is widespread in diatom type III metacaspases, but was not found in any other taxa. The characterization of a cell death associated protein in marine phytoplankton will enable deeper understanding of the ecological significance of PCD in bloom dynamics.

microbiology↗

bioRxiv2018

Nutrient deposition enhances post-fire survival in non-N-fixing savanna tree seedlings

Nutrient deposition can modify plant growth rates and potentially alter the susceptibility of plants to disturbance events, while also influencing properties of disturbance regimes. In mixed tree-grass ecosystems, such as savannas and tropical dry forests, tree seedling growth rates strongly influence the ability of seedlings to survive fire (i.e. post-fire seedling survival), and hence, vegetation structure and tree community composition. However the effects of nutrient deposition on the susceptibility of recruiting trees to fire are poorly quantified. In a field experiment, seedlings of multiple N-fixing and non-N-fixing tropical dry forest tree species were exposed to nitrogen (N) and phosphorus (P) fertilisation, and fire. We quantified nutrient-mediated changes in a) mean seedling growth rates; b) growth rates of the fastest growing individuals and c) post-fire seedling survival. N-fixers had substantially higher baseline post-fire seedling survival, that was unaffected by nutrient addition. Fertilisation, especially with N, increased post-fire survival probabilities in non-N-fixers by increasing the growth rates of the fastest growing individuals. These results suggest that fertilisation can lead to an increase in the relative abundance of non-N-fixers in the resprout community, and thereby, alter the community composition of tropical savanna and dry forest tree communities in the long-term.

ecology↗

bioRxiv2018

Revealing S-layer Functions in the Hyperthermophilic Crenarchaeon Sulfolobus islandicus

The crystalline surface layer (S-layer), consisting of two glycoproteins SlaA and SlaB, is considered to be the exclusive component of the cell envelope outside of the cytoplasmic membrane in Sulfolobus species. Although biochemically and structurally characterized, the S-layer in vivo functions remain largely elusive in Archaea. Here, we investigate how the S-layer genes contribute to the S-layer architecture and affect cellular physiology in a crenarchaeal model, Sulfolobus islandicus M.16.4. Electron micrographs of mutant cells lacking slaA or both slaA and slaB confirm the absence of the outermost layer (SlaA), whereas cells with intact, partially, or completely detached SlaA are observed for the {triangleup}slaB mutant. Importantly, we identify a novel S-layer-associated protein M164_1049, which does not functionally replace its homolog SlaB but likely assists SlaB to stabilize SlaA. Additionally, we find that mutants deficient in SlaA form large cell aggregates and the individual cell size varies significantly. The slaB gene deletion also causes noticeable cellular aggregation, but the size of those aggregates is smaller when compared to {triangleup}slaA and {triangleup}slaAB mutants. We further show the {triangleup}slaA mutant cells exhibit more sensitivity to hyperosmotic stress but are not reduced to wild-type cell size. Finally, we demonstrate that the {triangleup}slaA mutant contains aberrant chromosome copy numbers not seen in wild-type cells where the cell cycle is tightly regulated. Together these data suggest that the lack of slaA results in either cell fusion or irregularities in cell division. Our studies provide novel insights into the physiological and cellular functions of the S-layer in Archaea.\n\nSignificanceRediscovery of the ancient evolutionary relationship between archaea and eukaryotes has revitalized interest in archaeal cell biology. Key to understanding the archaeal cell is the S-layer which is ubiquitous in Archaea but whose in vivo function is unknown. In this study, we genetically dissect how the two well-known S-layer genes as well as a newly identified S-layer-associated-protein-encoding gene contribute to the S-layer architecture in a hyperthermophilic crenarchaeal model S. islandicus. We provide genetic evidence for the first time showing that the slaA gene is a key cell morphology determinant and may play a role in Sulfolobus cell division or cell fusion.

microbiology↗

bioRxiv2018

Transient arousal modulations are responsible for resting-state functional connectivity changes associated with head motion

Correlations of resting-state functional magnetic resonance imaging (rsfMRI) signals are being widely used for assessing functional brain connectivity in health and disease. However, an association was recently observed between rsfMRI connectivity modulations and the head motion parameters and regarded as a causal relationship, which has raised serious concerns about the validity of many rsfMRI findings. Here, we studied the origin of this rsfMRI-motion association and its relationship to arousal modulations. By using a template-matching method to locate arousal-related fMRI changes, we showed that the effects of high motion time points on rsfMRI connectivity are largely due to their significant overlap with arousal-affected time points. The finding suggests that the association between rsfMRI connectivity and the head motion parameters arises from their co-modulations at transient arousal modulations, and this information is critical not only for proper interpretation of motion-associated rsfMRI connectivity changes but also for controlling the potential confounding effects of arousal modulation on rsfMRI metrics.

neuroscience↗

bioRxiv2018

Microbial and Metabolic Succession on Common Building Materials Under High Humidity Conditions

Despite considerable efforts to characterize the ecology of bacteria and fungi in the built environment (BE), the metabolic mechanisms underpinning their colonization and successional dynamics remain unclear. Here, we applied bacterial/viral particle counting, qPCR, 16S and ITS rRNA amplicon sequencing, and metabolomics to longitudinally characterize the ecological dynamics of four commonly used building materials maintained at high humidity conditions (~94% RH). We varied the natural inoculum provided to each material by placing them in different occupied spaces, and we wet the surface of half of the samples of each material to simulate a flooding event. As expected, different materials showed different bacterial and viral particle abundance, with wet materials having higher growth rates and lower alpha diversity compared to non-wetted materials. Wetting described the majority of the variance in bacterial, fungal and metabolite structure, and material type only influenced bacterial and metabolic diversity, while location of inoculation was only weakly associated with bacterial and fungal beta diversity. Metabolites indicative of microbial activity were identified, as were those that were native to the surface material. Glucose-phosphate was abundant on all materials (except mold-free gypsum) and was correlated with Enterobacteriaceae, which could indicate a potential bacterial nutrient source. A compound consistent with scopoletin, a plant metabolite with antimicrobial activity, was significantly negatively correlated with Bacillus and positively correlated with Pseudomonas and enriched in medium density fiberboard (MDF) materials. In wet samples, the alkaloids nigragillin and fumigaclavine C, both with antimicrobial properties, were significantly positively correlated with the fungal phylum Ascomycota. Nigragillin, was also negatively correlated with Bacillus and Pseudomonas abundance. Thiabendazole and azoxystrobin (anti-fungal compounds) were highly abundant on mold-resistant gypsum wallboard and likely directly influenced the decreased fungal growth observed on this material. The mold-resistant gypsum material also showed a significant increase in bacterial alpha diversity, and bacterial and viral particle abundance, as well as a decrease in metabolite diversity, likely a result of reduced fungal growth. Penicillium taxa were positively correlated with thiabendazole, which suggested the persistence of resistant strains. Also, specific to the wet samples, Bacillus abundance was positively correlated with the azoxystrobin, suggesting bi-directional competitive adaptation, and positively correlated with metabolites known to interfere with Pseudomonas biofilm formation, which could explain the anti-correlation between these taxa. As expected, high moisture conditions enabled faster growth of inoculating microorganisms, whose composition, chemistry, and competition was shaped by surface material, suggesting that both fungal and bacterial growth need to be considered when determining the impact of dampness in built environments.

microbiology↗

bioRxiv2018

A Simple Approximation To The Bias Of Gene-Environment Interactions In Case/Control Studies With Silent Disease

One of the most important research areas in case-control Genome-Wide Association Studies is to determine how the effect of a genotype varies across the environment or to measure the gene-environment interaction (GxE). We consider the scenario when some of the \"healthy\" controls actually have the disease and when the frequency of these latent cases varies by the environmental variable of interest. In this scenario, performing logistic regression of clinically defined case status on the genetic variant, environmental variable, and their interaction will result in biased estimates of GxE interaction. Here, we derive a general theoretical approximation to the bias in the estimates of the GxE interaction and show, through extensive simulation, that this approximation is accurate in finite samples. Moreover, we apply this approximation to evaluate the bias in the effect estimates of the genetic variants related to mitochondrial proteins a large-scale Prostate Cancer study.

genetics↗