Biology subjects

Finnegan, P. M.

Publications and source records attributed to Finnegan, P. M..

3 recordsLinked to original sources

bioRxiv2025

Diet, Climatic Conditions, and Sex Affect the Mycobiome of Wild Common Marmosets (Callithrix jacchus)

Recent research on the gut mycobiome, or the fungal portion of the gut microbial community, suggests that it interacts with host physiology and impacts host health. However, fundamental questions about how the mycobiome is assembled remain unanswered. It remains unclear whether the fungi detected in the gut are predominantly residents of the gastrointestinal tract or if they are largely transient and pass through. To address this question, we sought to determine whether host factors (e.g., sex) or external environmental factors (e.g., variable climatic conditions and diet) were more strongly correlated with the gut mycobiome of common marmosets (Callithrix jacchus), a primate species living in the semi-arid Caatinga biome of northeastern Brazil. A stronger correlation with host factors, would suggest a more resident mycobiome, while a stronger association with external environmental factors suggests a more transient mycobiome. We collected 52 marmoset fecal samples across a 2-year period and DNA metabarcoding was used to assess both the mycobiome and diet of each sample. We used FUNGuild to assign ecological roles to the fungi, which were sorted into resident (e.g. animal pathogens) and transient (e.g. plant pathogens) groups. We found that mycobiome richness and evenness varied by host sex and correlated with the arthropod component of the diet while mycobiome composition varied between wetter and drier periods and correlated with the plant portion of the diet. The fact that external environmental factors were associated with the presence of specific taxa led us to conclude that the mycobiome is largely made up of transient taxa. ImportanceOther than causing infectious diseases, the function of the mycobiome is poorly understood. There is evidence that the mycobiome can play a positive role, such as training the hosts immune system, and a negative role, such as causing cancer and Alzheimers disease. To fully understand these associations, basic questions about which taxa live in the host and which pass through, must be addressed. We used DNA metabarcoding and a tool that can group fungi based on their ecological roles, to determine whether the mycobiome of Caatinga marmosets was more strongly correlated with host sex or host diet and environment. We found that the marmoset mycobiome was more strongly correlated with diet and environment and most fungi passed through the host rather than lived in the hosts gut.

microbiology↗

bioRxiv2022

Functional antibodies exhibit light chain coherence

The vertebrate adaptive immune system modifies the genome of individual B cells to encode antibodies binding particular antigens1. In most mammals, antibodies are composed of a heavy and a light chain which are sequentially generated by recombination of V, D (for heavy chains), J, and C gene segments. Each chain contains three complementarity-determining regions (CDR1-3), contributing to antigen specificity. Certain heavy and light chains are preferred for particular antigens2-21. We considered pairs of B cells sharing the same heavy chain V gene and CDRH3 amino acid sequence and isolated from different donors, also known as public clonotypes22,23. We show that for naive antibodies (not yet adapted to antigens), the probability that they use the same light chain V gene is [~]10%, whereas for memory (functional) antibodies it is [~]80%. This property of functional antibodies is a phenomenon we call light chain coherence. We also observe it when similar heavy chains recur within a donor. Thus, though naive antibodies appear to recur by chance, the recurrence of functional antibodies reveals surprising constraint and determinism in the processes of V(D)J recombination and immune selection. For most functional antibodies, the heavy chain determines the light chain.

immunology↗

bioRxiv2022

enclone: precision clonotyping and analysis of immune receptors

Half a billion years of evolutionary battle forged the vertebrate adaptive immune system, an astonishingly versatile factory for molecules that can adapt to arbitrary attacks. The history of an individual encounter is chronicled within a clonotype: the descendants of a single fully rearranged adaptive immune cell. For B cells, reading this immune history for an individual remains a fundamental challenge of modern immunology. Identification of such clonotypes is a magnificently challenging problem for three reasons: O_LIThe cell history is inferred rather than directly observed: the only available data are the sequences of V(D)J molecules occurring in a sample of cells. C_LIO_LIEach immune receptor is a pair of V(D)J molecules. Identifying these pairs at scale is a technological challenge and cannot be done with perfect accuracy--real samples are mixtures of cells and fragments thereof. C_LIO_LIThese molecules can be intensely mutated during the optimization of the response to particular antigens, blurring distinctions between kindred molecules. C_LI It is thus impossible to determine clonotypes exactly. All solutions to this problem make a trade-off between sensitivity and specificity; useful solutions must address actual artifacts found in real data. We present enclone1, a system for computing approximate clonotypes from single cell data, and demonstrate its use and value with the 10x Genomics Immune Profiling Solution. To test it, we generate data for 1.6 million individual B cells, from four humans, including deliberately enriched memory cells, to tax the algorithm and provide a resource for the community. We analytically determine the specificity of enclones clonotyping algorithm, showing that on this dataset the probability of co-clonotyping two unrelated B cells is around 10-9. We prove that using only heavy chains increases the error rate by two orders of magnitude. enclone comprises a comprehensive toolkit for the analysis and display of immune receptor data. It is ultra-fast, easy to install, has public source code, comes with public data, and is documented at bit.ly/enclone. It has three "flavors" of use: (1) as a command-line tool run from a terminal window, that yields visual output; (2) as a command-line tool that yields parseable output that can be fed to other programs; and (3) as a graphical version (GUI).

immunology↗