Biology subjects

Hernandez, L.

Publications and source records attributed to Hernandez, L..

22 records · Page 2Linked to original sources

bioRxiv2019

Unmasking the tissue microecology of ductal carcinoma in situ with deep learning

Despite increasing evidence supporting the clinical relevance of tumour infiltrating lymphocytes (TILs) in invasive breast cancer, TIL spatial distribution pattern surrounding ductal carcinoma in situ (DCIS) and its association with progression is not well understood. To characterize the tissue microecology of DCIS, we designed and tested a new deep learning pipeline, UNMaSk (UNet-IM-Net-SCCNN), for the automated detection and simultaneous segmentation of DCIS ducts. This new method achieved the highest sensitivity and recall over cutting-edge deep learning networks in three patient cohorts, as well as the highest concordance with DCIS identification based on CK5 staining. Following automated DCIS detection, spatial tessellation centred at each DCIS duct created the boundary in which local ecology can be studied. Single cell identification and classification was performed with an existing deep learning method to map the distribution of TILs. In a dataset comprising grade 2-3 pure DCIS and DCIS adjacent to invasive cancer (adjacent DCIS), we found that pure DCIS cases had more TILs compared to adjacent DCIS. However, TILs co-localise significantly less with DCIS ducts in pure DCIS compared with adjacent DCIS, suggesting a more inflamed tissue ecology local to adjacent DCIS cases. Our experiments demonstrate that technological developments in deep convolutional neural networks and digital pathology can enable us to automate the identification of DCIS as well as to quantify the spatial relationship with TILs, providing a new way to study immune response and identify new markers of progression, thereby improving clinical management.

pathology↗

bioRxiv2019

Polymorphism analyses and protein modelling inform on functional specialization of Piwi clade genes in the arboviral vector Aedes albopictus

Current knowledge of the piRNA pathway is based mainly on studies on the model organism Drosophila melanogaster, where three proteins of the Piwi subclade of the Argonaute family interact with PIWI-interacting RNAs to silence transposable elements in gonadal tissues. In mosquito species that transmit epidemic arboviruses such as the Dengue and Chikungunya viruses, Piwi clade genes underwent expansion, are also expressed in the soma, and code for proteins that may elicit antiviral functions and crosstalk with other proteins of recognized antiviral mechanisms. These observations underline the importance of expanding our knowledge of the piRNA pathway beyond D. melanogaster.\n\nHere we focus on the emerging arboviral vector Aedes albopictus and we couple traditional approaches of expression and adaptive evolution analyses with most current computational predictions of protein structure to study evolutionary divergence among Piwi clade proteins. Superposition of protein homology models indicate high structure similarity among all Piwi proteins, with high levels of amino acid conservation in the inner regions devoted to RNA binding. On the contrary, solvent-exposed surfaces showed low conservation, with several sites under positive selection. Expression profiles of Piwi transcripts during mosquito development and after infection with the Dengue 1 virus showed a concerted elicitation of all Piwi transcripts during viral dissemination, while the maintenance of infection primarily relied on the expression of Piwi5. In contrast, establishment of persistent infection by the Chikungunya virus is accompanied by an increased expression of all Piwi genes, particularly Piwi4 and, again, Piwi5. Overall these results are consistent with functional specialization and a general antiviral role for Piwi5. Experimental evidences of sites under positive selection in Piwi1/3, Piwi4 and Piwi6, further provide useful knowledge to design tailored functional experiments.\n\nAuthor summaryArgonautes are ancient proteins involved in many cellular processes, including innate immunity. Early in eukaryote evolution, Argonautes separated into Ago and Piwi clades, which maintain a dynamic evolutionary history with frequent duplications and losses. The use of Drosophila melanogaster as a model organism proved fundamental to understand the function of Argonautes. However, recent studies showed that the patterns and observations made in D. melanogaster, including the number of Argonautes, their expression profile and their function, are a rarity among Dipterans.\n\nIn vectors of epidemic arboviruses such as Dengue and Chikungunya viruses, Piwi genes underwent expansion, are expressed in the soma, and some of them appear to have antiviral functions. Besides being an important basic question, the identification of which (and how) Piwi genes have antiviral functions may be used for the development of novel genetic-based strategies of vector control. Here we coupled population genetics models with computational predictions of protein structure and expression analyses to investigate the evolution and function of Piwi genes of the emerging vector Aedes albopictus. Our data support a general antiviral role for Piwi5. Instead, the detection of complex expression profiles with the presence of sites under positive selection in Piwi1/3, Piwi4 and Piwi6 requires tailored functional experiments to clarify their antiviral role.

evolutionary biology↗

bioRxiv2018

Pattern of severe injuries in Spanish children: boys and falls are alarmingly overrepresented

Background: Taking into account that injury is one of the main causes of child fatalities in developed countries, and that boys are more likely to suffer it than girls, we have explored a database of pediatric patients with severe injuries to determine whether sex and age influence the pattern of these fatalities, and the magnitude of this.\n\nMethod: Observational study of the demographic and clinical characteristics of 227 patients from a Spanish pediatric reference hospital, all of them admitted with a diagnosis of trauma.\n\nResult: Falls are the most frequent type of trauma (60.7%), followed by pedestrian traffic collisions (15%). Boys are over-represented in falls (72% vs 28% in girls) and pedestrian traffic injuries (61% vs 39 %). In boys, falls are mainly observed in public roads and during leisure activities (53.8%) whereas in girls at home (55.2%). In a logistic regression, sex and age are statistically significant predictors of severe trauma, boys (OR = 1.59) and the adolescent age group (OR = 3.7) showed the highest odds.\n\nConclusion: We have observed a clear gender-biased pattern of injury-related events: falls are the leading cause of injuries, with 2.5 boys for every girl. Falls mostly happened during outdoor leisure activities in boys and at home in girls. Pedestrian traffic injuries also show significant differences between sexes, emphasizing the role of cognitive and cultural factors in childrens behavior.

epidemiology↗

bioRxiv2017

Breaking the spell of nestedness

Mutualistic interactions, which are beneficial for both interacting species, are recurrently present in ecosystems. Observations of natural systems showed that, if we draw mutualistic relationships as binary links between species, the resulting bipartite network of interactions displays a widespread particular ordering called nestedness [1]. On the other hand, theoretical works have shown that a nested structure has a positive impact on a number of relevant features ranging from species coexistence [2], to a higher structural stability of communities and biodiversity [3,4]. However, how nestedness emerges and what are its determinants, are still open challenges that have led to multiple debates to date [5-7]. Here, we show, by applying a theoretical approach to the analysis of 167 real mutualistic networks, that nestedness is not an irreducible feature, but a consequence of the degree sequences of both guilds of the mutualistic network. Remarkably, we find that an outstanding majority of the analyzed networks does not show statistical significant nestedness. These findings point to the need of revising previous claims about the role of nestedness and might contribute to expand our understanding of how evolution shapes mutualistic interactions and communities by placing the focus on the local properties rather than on global quantities.

ecology↗