Biology subjects

Berry, A. A.

Publications and source records attributed to Berry, A. A..

7 recordsLinked to original sources

bioRxiv2026

Comprehensive characterization of Plasmodium vivax antigens using a high-density peptide array

Plasmodium vivax is the second most prevalent Plasmodium species, with 2.5 billion people at risk of infection worldwide and around 10 million cases of clinical vivax malaria every year. Despite the clinical importance of this pathogen, very little is known about the P. vivax proteins recognized by the host immune system, which hinders our ability to select vaccine candidates or develop efficient serological markers. To comprehensively characterize immunogenic P. vivax proteins, we designed a high-density peptide array containing 4.2 million peptides covering the entire protein sequence of all P. vivax genes and analyzed antibody responses of infected and malaria-naive individuals. We identified a total of 283 proteins that are commonly immunogenic in symptomatic individuals. These proteins included most proteins known to be involved in erythrocyte invasion, a putative new invasion protein, several nucleoporins, and many uncharacterized proteins that should be further investigated for their roles during blood-stage infections. These analyses also revealed a unique pattern of antibody response against PIR proteins in asymptomatic individuals, that could be associated with protection against clinical vivax malaria. Overall, these data provide an agnostic and comprehensive perspective on immunogenic P. vivax proteins and constitute an important resource for the malaria community to develop new tools for better detecting and eliminating this important human pathogen.

microbiology↗

bioRxiv2024

Immune gene expression changes more during a malaria transmission season than between consecutive seasons.

Plasmodium parasites caused over 600,000 deaths in 2022. In Mali, P. falciparum is responsible for the majority of malaria cases and deaths and is transmitted seasonally. Anti-malarial immunity develops slowly over repeated exposures to P. falciparum but some aspects of this immunity (e.g., antibody titers) wane during the non-transmission, dry season. Here, we sequenced RNA from 33 pediatric blood samples collected during P. falciparum infections at the beginning or end of a transmission season and characterized the host and parasite gene expression profiles of paired, consecutive infections. Our analyses showed that human gene expression changes more over the course of one transmission season than it does between seasons, with signatures consistent with the partial development of adaptive immunity during one transmission season, contrasting with the stability in gene expression during the dry season. By contrast, P. falciparum gene expression did not seem to vary significantly and remained stable both across and between seasons. Overall, our results provide novel insights into the dynamics of anti-malarial immunity development over short timeframes.

bioinformatics↗

bioRxiv2023

Gene expression analyses reveal differences in children's response to malaria according to their age

In Bandiagara, Mali, children experience on average two clinical malaria episodes per season. However, even in the same transmission area, the number of uncomplicated symptomatic infections, and their parasitemia, vary dramatically among children. To examine the factors contributing to these variations, we simultaneously characterized the host and parasite gene expression profiles from 136 children with symptomatic falciparum malaria and analyzed the expression of 9,205 human and 2,484 Plasmodium genes. We used gene expression deconvolution to estimate the relative proportion of immune cells and parasite stages in each sample and to adjust the differential gene expression analyses. Parasitemia explained much of the variation in both host and parasite gene expression and revealed that infections with higher parasitemia had more neutrophils and fewer T cells, suggesting parasitemia-dependent neutrophil recruitment and/or T cell extravasation to secondary lymphoid organs. The childs age was also strongly correlated with gene expression variations. Plasmodium falciparum genes associated with age suggested that older children carried more male gametocytes, while host genes associated with age indicated a stronger innate response (through TLR and NLR signaling) in younger children and stronger adaptive immunity (through TCR and BCR signaling) in older children. These analyses highlight the variability in host responses and parasite regulation during P. falciparum symptomatic infections and emphasize the importance of considering the childrens age when studying and treating malaria infections. One Sentence SummaryHuman and P. falciparum gene expression differs according to the infections parasitemia and the childs age, highlighting an age-dependent response to malaria and complex cellular and molecular -host/parasite interactions.

microbiology↗

bioRxiv2022

Malian children infected with Plasmodium ovale and Plasmodium falciparum display very similar gene expression profiles.

Plasmodium parasites caused 241 million cases of malaria and over 600,000 deaths in 2020. Both P. falciparum and P. ovale are endemic to Mali and cause malaria illness, with P. falciparum infections typically being more severe. Here, we sequenced RNA from nine pediatric blood samples collected during uncomplicated, symptomatic infections with either P. falciparum or P. ovale and characterized the host and parasite gene expression profiles. We found that human gene expression varies more between individuals than according to the parasite species causing the infection, while parasite gene expression profiles cluster by species. Additionally, we characterized DNA polymorphisms of the parasites directly from the RNA-seq reads and found comparable levels of genetic diversity in both species despite dramatic differences in prevalence. Our results provide unique insights into host-pathogen interactions during malaria infections and their variations according to the infecting Plasmodium species, which will be critical to develop better elimination strategies against all human Plasmodium parasites. Author SummaryMultiple species of Plasmodium parasites can cause human malaria. Most studies and elimination efforts target P. falciparum, the most common cause of malaria worldwide and the species responsible for the vast majority of the mortality. Other Plasmodium species, such as P. ovale, typically lead to less severe forms of the disease but little is known about the molecular mechanisms at play during malaria infections with different parasites. We analyzed host and parasite gene expression from children successively infected with P. ovale and P. falciparum and found that, while the parasite gene expression differed significantly, the transcriptional profiles of the host immune cells were similar in P. ovale or P. falciparum infections. This suggests that infected individuals respond to uncomplicated malaria infections similarly, regardless of the Plasmodium species causing the infection, and that alternative immune processes may become important during the progression to severe P. falciparum malaria (rather than being inherent features of P. falciparum infections). Additionally, we observed similar levels of genetic diversity among P. ovale and P. falciparum parasites, suggesting that the P. ovale population might be larger than currently thought, possibly due to extensive misdiagnosis or the existence of hidden reservoirs of parasites.

microbiology↗

bioRxiv2022

Morphological and sensorimotor phenotypes in a zebrafish CHARGE syndrome model are domain-dependent

CHARGE syndrome is a rare disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from de novo, loss-of-function mutations in a master transcriptional regulator, chromodomain-helicase-DNA-binding-protein-7 (CHD7). CHD7 regulates key neurodevelopmental factors and is required for neural processes including neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant chd7 zebrafish line using CRISPR/Cas9 that recapitulates multiple CHARGE phenotypes. Using a panel of behavioral assays, we find that chd7 mutants have specific auditory and visually driven behavioral deficits that are independent of defects in sensory structures, implicating chd7 in the regulation of underlying brain circuits. Furthermore, by analyzing multiple chd7 alleles we show that the penetrance of morphological and behavioral phenotypes depends on the mutation location. These results provide novel insight into the heterogeneity of CHARGE syndrome and will inform future work to define mechanisms of CHD7-dependent neurobehavioral symptoms. Summary statementMutation location within chd7 affects the expression of CHARGE Syndrome-related morphological and behavioral phenotypes in a larval zebrafish CHARGE model.

neuroscience↗

bioRxiv2020

Atypical B cells are a normal component of immune responses to vaccination and infection in humans

The full diversity of the circulating human B cell compartment is unknown. Flow cytometry analysis suggests that in addition to naive and memory B cells, there exists a population of CD11c+, CD27- CD21- "atypical" B cells, that are associated with chronic or recurrent infection and autoimmunity. We used single cell RNA-seq approaches to examine the diversity of both antigen-specific B cells and total B cells in healthy subjects and individuals naturally-exposed to recurrent malaria infections. This analysis revealed two B cell lineages: a classical lineage of activated and resting memory B cells, and an atypical-like lineage. Surprisingly, the atypical lineage was common in both malaria exposed individuals and non-exposed healthy controls. Using barcoded antibodies in conjunction with our transcriptomic data, we found that atypical lineage cells in healthy individuals lack many atypical B markers and thus represent an undercounted cryptic population. We further determined using antigen specific probes that atypical cells can be induced by primary vaccination in humans and can be recalled upon boosting. Collectively these data suggest that atypical cells are not necessarily pathogenic but can be a normal component of B responses to antigen.

immunology↗

bioRxiv2019

The epigenomic landscape regulating organogenesis in human embryos linked to developmental disorders

How the genome activates or silences transcriptional programmes governs organ formation. Little is known in human embryos undermining our ability to benchmark the fidelity of in vitro stem cell differentiation or cell programming, or interpret the pathogenicity of noncoding variation. Here, we studied histone modifications across thirteen tissues during human organogenesis. We integrated the data with transcription to build the first overview of how the human genome differentially regulates alternative organ fates including by repression. Promoters from nearly 20,000 genes partitioned into discrete states without showing bivalency. Key developmental gene sets were actively repressed outside of the appropriate organ. Candidate enhancers, functional in zebrafish, allowed imputation of tissue-specific and shared patterns of transcription factor binding. Overlaying more than 700 noncoding mutations from patients with developmental disorders allowed correlation to unanticipated target genes. Taken together, the data provide a new, comprehensive genomic framework for investigating normal and abnormal human development.

genomics↗