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Biology subjects

Janecka, M.

Publications and source records attributed to Janecka, M..

2 recordsLinked to original sources

Artificial Selection and the Skin Microbiome Independently Predict Parasite Resistance

Host responses to parasite infection involve several interacting systems. Host genetics determine much of the response, but it is increasingly clear that the host-associated microbiome also plays a role. Genetically determined systems and the microbiome can also interact; for example, the microbiome can modulate the immune response, and vice versa. However, it remains unclear how such interactions between the host immune system and the microbiome may influence the hosts overall response to parasites. To investigate how host genetics and the microbiome interact to shape responses to parasites, we imposed truncation selection on Trinidadian guppies (Poecilia reticulata) for low and high resistance to the specialist ectoparasite Gyrodactylus turnbulli. After 3-6 generations of breeding without parasites, we sampled the skin-associated microbiome and infected fish from each line. We applied Dirichlet Multinomial Modeling (DMM) machine-learning to identify bacterial community types across lines and evaluated how selection line and community type explained variations in infection severity. Our findings showed that among females, the resistant line had significantly lower infection severity, while the susceptible line had higher infection severity. Among males, only the susceptible line experienced higher infection severity compared to the other lines. Line did not explain skin microbial diversity, structure or composition. Our DMM analysis revealed three distinct bacterial community types, independent of artificial selection lines, which explained just as much variation in infection load as selection line. Overall, we found that the microbiome and host genetics independently predict infection severity, highlighting the microbiomes active role in host-parasite interactions.

ecology↗

Assessing the burden of rare DNA methylation outliers in schizophrenia

Along with case-control group differences in DNA methylation (DNAm) identified in epigenomewide association studies (EWAS), multiple rare DNAm outliers may exist in subsets of cases, underlying the etiological heterogeneity of some disorders. This creates an impetus for novel approaches focused on detecting rare/private outliers in the individual methylomes. Here, we present a novel, data-driven method - Outlier Methylation Analysis (OMA) - which through optimization detects genomic regions with strongly deviating DNAm levels, which we call outlier methylation regions (OMRs). Focusing on schizophrenia (SCZ) - a neuropsychiatric disorder with a heterogeneous etiology - we applied the OMA method in two independent, publicly available SCZ case-control samples with DNAm array information. We found SCZ cases had an increased burden of OMRs compared to controls (IRR=1.22, p=1.8x10-8), and case OMRs were enriched in regions relevant to cellular differentiation and development (i.e. polycomb repressed elements in the Gm12878 differentiated cell line, p=1.9x10-5, and poised promoters in the H1hesc stem cell line, p=5.4x10-4). Furthermore, SCZ cases were ~2.5-fold enriched (p=1.1x10-3) for OMRs overlapping genesets associated with developmental processes. The OMR burden was reduced in clozapine-treated, compared to untreated, SCZ cases (IRR=0.88, p=9.5x10-3), and also associated with increased chronological age (IRR=1.01, p= 2.7x10-16). Our findings demonstrate an elevated burden of OMRs in SCZ, implying methylomic dysregulation in SCZ which could correspond to the etiological heterogeneity among cases. These results remain to be causally examined and replicated in other cohorts and tissues. For this, and applications in other traits, we offer the OMA method to the scientific community.

genetics↗