Biology subjects

Solomon, A.

Publications and source records attributed to Solomon, A..

3 recordsLinked to original sources

bioRxiv2017

Reconstruction of developmental landscapes by optimal-transport analysis of single-cell gene expression sheds light on cellular reprogramming.

Understanding the molecular programs that guide cellular differentiation during development is a major goal of modern biology. Here, we introduce an approach, WADDINGTON-OT, based on the mathematics of optimal transport, for inferring developmental landscapes, probabilistic cellular fates and dynamic trajectories from large-scale single-cell RNA-seq (scRNA-seq) data collected along a time course. We demonstrate the power of WADDINGTON-OT by applying the approach to study 65,781 scRNA-seq profiles collected at 10 time points over 16 days during reprogramming of fibroblasts to iPSCs. We construct a high-resolution map of reprogramming that rediscovers known features; uncovers new alternative cell fates including neuraland placental-like cells; predicts the origin and fate of any cell class; highlights senescent-like cells that may support reprogramming through paracrine signaling; and implicates regulatory models in particular trajectories. Of these findings, we highlight Obox6, which we experimentally show enhances reprogramming efficiency. Our approach provides a general framework for investigating cellular differentiation.

bioinformatics↗

bioRxiv2017

Age-specific prevalence of anti-Pgp3 antibodies and severe conjunctival scarring in the Solomon Islands

BackgroundTrachomatous trichiasis (TT) and ocular Chlamydia trachomatis (Ct) infection in the Solomon Islands are scarce, whereas trachomatous inflammation-follicular (TF) is prevalent.\n\nMethodsWe enrolled 1511 people aged [≥]1 year from randomly selected households in 13 villages in which >10% of the population had TF prior to a single round of azithromycin MDA undertaken six months previously. Blood was collected from people of all ages to be screened for anti-Pgp3 antibodies. Photographs were collected from people of all ages for analysis of scarring severity.\n\nResultsConjunctival scars were visible in 13.1% of photographs. Mild (p<0.0001) but not severe (p=0.149) scars increased in prevalence with age. Anti-Pgp3 antibody seroprevalence was 18% in 1-9 year olds, increased sharply around the age of sexual debut, and reached 69% in those over 25 years. Anti-Pgp3 seropositivity did not increase significantly between the ages of 1-9 years, and was not associated with scarring in children (p=0.472) or TF in children (p=0.581).\n\nConclusionsSigns of trachoma are common in the Solomon Islands but occur frequently in individuals who have no serological evidence of prior ocular infection with Ct. WHO recommendations for directing MDA provision based on signs alone may not be suitable in this context.

epidemiology↗

bioRxiv2017

Active Trachoma Cases In The Solomon Islands Have Varied Polymicrobial Community Structures But Do Not Associate With Individual Non-Chlamydial Pathogens Of The Eye

BackgroundSeveral non-chlamydial microbial pathogens are associated with clinical signs of active trachoma in trachoma-endemic communities with a low prevalence of ocular Chlamydia trachomatis (Ct) infection. In the Solomon Islands, the prevalence of Ct among children is low despite the prevalence of active trachoma being moderate. We therefore set out to investigate whether active trachoma was associated with a common non-chlamydial infection or with a dominant polymicrobial community dysbiosis in the Solomon Islands.\n\nMethodsWe studied DNA from conjunctival swabs collected from 257 Solomon Islanders with active trachoma and matched controls. Droplet digital PCR was used to test for pathogens suspected to be able to induce follicular conjunctivitis. Polymicrobial community diversity and composition were studied by sequencing of hypervariable regions of the 16S ribosomal ribonucleic acid gene in a subset of 54 cases and 53 controls.\n\nResultsAlthough Ct was associated with active trachoma, the number of infections was low (cases: 3.9%, controls: 0.4%). Estimated prevalence (cases, controls) of each non-chlamydial infection was as follows: S. aureus (1.9%, 1.9%), Adenoviridae (1.2%, 1.2%), coagulase-negative Staphylococcus (5.8%, 4.3%), H. influenzae (7.4%, 11.7%), M. catarrhalis (2.3%, 4.7%) and S. pneumoniae (7.0%, 6.2%). There was no statistically significant association between clinical signs of trachoma and presence or load of any of the non-Ct infections that were assayed. Inter-individual variations in the conjunctival microbiome were characterised by differences in the levels of Corynebacterium, Proprionibacterium, Helicobacter and Paracoccus, but diversity and relative abundance of these specific genera did not differ significantly between cases and controls.\n\nDiscussionIt is unlikely that the prevalent trachoma-like follicular conjunctivitis in the Solomon Islands has a dominant bacterial aetiology. Before implementing community-wide azithromycin distribution for trachoma, policy makers should consider that clinical signs of trachoma can be observed in the absence of any detectable azithromycin-susceptible organism.

microbiology↗