Pedro Ferreira

Molecular signatures of plastic phenotypes in two eusocial insect species with simple societies

Significance In eusocial insect societies, such as ants and some bees and wasps, phenotypes are highly plastic, generating alternative phenotypes (queens and workers) from the same genome. The greatest plasticity is found in simple insect societies, in which individuals can switch between phenotypes as adults. The genomic, transcriptional, and epigenetic underpinnings of such plasticity are largely unknown. In contrast to the complex societies of the honeybee, we find that simple insect societies lack distinct transcriptional differentiation between phenotypes and coherently patterned DNA methylomes. Instead, alternative phenotypes are largely defined by subtle transcriptional network organization. These traits may facilitate genomic plasticity. These insights and resources will stimulate new approaches and hypotheses that will help to unravel the genomic processes that create phenotypic plasticity. Phenotypic plasticity is important in adaptation and shapes the evolution of organisms. However, we understand little about what aspects of the genome are important in facilitating plasticity. Eusocial insect societies produce plastic phenotypes from the same genome, as reproductives (queens) and nonreproductives (workers). The greatest plasticity is found in the simple eusocial insect societies in which individuals retain the ability to switch between reproductive and nonreproductive phenotypes as adults. We lack comprehensive data on the molecular basis of plastic phenotypes. Here, we sequenced genomes, microRNAs (miRNAs), and multiple transcriptomes and methylomes from individual brains in a wasp (Polistes canadensis) and an ant (Dinoponera quadriceps) that live in simple eusocial societies. In both species, we found few differences between phenotypes at the transcriptional level, with little functional specialization, and no evidence that phenotype-specific gene expression is driven by DNA methylation or miRNAs. Instead, phenotypic differentiation was defined more subtly by nonrandom transcriptional network organization, with roles in these networks for both conserved and taxon-restricted genes. The general lack of highly methylated regions or methylome patterning in both species may be an important mechanism for achieving plasticity among phenotypes during adulthood. These findings define previously unidentified hypotheses on the genomic processes that facilitate plasticity and suggest that the molecular hallmarks of social behavior are likely to differ with the level of social complexity.

Evolutionary patterns at the RNase based gametophytic self - incompatibility system in two divergent Rosaceae groups (Maloideae and Prunus)

BackgroundWithin Rosaceae, the RNase based gametophytic self-incompatibility (GSI) system has been studied at the molecular level in Maloideae and Prunus species that have been diverging for, at least, 32 million years. In order to understand RNase based GSI evolution within this family, comparative studies must be performed, using similar methodologies.ResultIt is here shown that many features are shared between the two species groups such as levels of recombination at the S-RNase (the S-pistil component) gene, and the rate at which new specificities arise. Nevertheless, important differences are found regarding the number of ancestral lineages and the degree of specificity sharing between closely related species. In Maloideae, about 17% of the amino acid positions at the S-RNase protein are found to be positively selected, and they occupy about 30% of the exposed protein surface. Positively selected amino acid sites are shown to be located on either side of the active site cleft, an observation that is compatible with current models of specificity determination. At positively selected amino acid sites, non-conservative changes are almost as frequent as conservative changes. There is no evidence that at these sites the most drastic amino acid changes may be more strongly selected.ConclusionsMany similarities are found between the GSI system of Prunus and Maloideae that are compatible with the single origin hypothesis for RNase based GSI. The presence of common features such as the location of positively selected amino acid sites and lysine residues that may be important for ubiquitylation, raise a number of issues that, in principle, can be experimentally addressed in Maloideae. Nevertheless, there are also many important differences between the two Rosaceae GSI systems. How such features changed during evolution remains a puzzling issue.

Predicting malignancy from mammography findings and image-guided core biopsies

The main goal of this work is to produce machine learning models that predict the outcome of a mammography from a reduced set of annotated mammography findings. In the study we used a dataset consisting of 348 consecutive breast masses that underwent image guided core biopsy performed between October 2005 and December 2007 on 328 female subjects. We applied various algorithms with parameter variation to learn from the data. The tasks were to predict mass density and to predict malignancy. The best classifier that predicts mass density is based on a support vector machine and has accuracy of 81.3%. The expert correctly annotated 70% of the mass densities. The best classifier that predicts malignancy is also based on a support vector machine and has accuracy of 85.6%, with a positive predictive value of 85%. One important contribution of this work is that our model can predict malignancy in the absence of the mass density attribute, since we can fill up this attribute using our mass density predictor.

The effects of death and post-mortem cold ischemia on human tissue transcriptomes

Post-mortem tissues samples are a key resource for investigating patterns of gene expression. However, the processes triggered by death and the post-mortem interval (PMI) can significantly alter physiologically normal RNA levels. We investigate the impact of PMI on gene expression using data from multiple tissues of post-mortem donors obtained from the GTEx project. We find that many genes change expression over relatively short PMIs in a tissue-specific manner, but this potentially confounding effect in a biological analysis can be minimized by taking into account appropriate covariates. By comparing ante- and post-mortem blood samples, we identify the cascade of transcriptional events triggered by death of the organism. These events do not appear to simply reflect stochastic variation resulting from mRNA degradation, but active and ongoing regulation of transcription. Finally, we develop a model to predict the time since death from the analysis of the transcriptome of a few readily accessible tissues.RNA levels in post-mortem tissue can differ greatly from those before death. Studying the effect of post-mortem interval on the transcriptome in 36 human tissues, Ferreira et al. find that the response to death is largely tissue-specific and develop a model to predict time since death based on RNA data.

Predicting Malignancy from Mammography Findings and Surgical Biopsies

Breast screening is the regular examination of a womans breasts to find breast cancer earlier. The sole exam approved for this purpose is mammography. Usually, findings are annotated through the Breast Imaging Reporting and Data System (BIRADS) created by the American College of Radiology. The BIRADS system determines a standard lexicon to be used by radiologists when studying each finding. Although the lexicon is standard, the annotation accuracy of the findings depends on the experience of the radiologist. Moreover, the accuracy of the classification of a mammography is also highly dependent on the expertise of the radiologist. A correct classification is paramount due to economical and humanitarian reasons. The main goal of this work is to produce machine learning models that predict the outcome of a mammography from a reduced set of annotated mammography findings. In the study we used a data set consisting of 348 consecutive breast masses that underwent image guided or surgical biopsy performed between October 2005 and December 2007 on 328 female subjects. The main conclusions are threefold: (1) automatic classification of a mammography, independent on information about mass density, can reach equal or better results than the classification performed by a physician, (2) mass density seems to be a good indicator of malignancy, as previous studies suggested, (3) a machine learning model can predict mass density with a quality as good as the specialist blind to biopsy, which is one of our main contributions. Our model can predict malignancy in the absence of the mass density attribute, since we can fill up this attribute using our mass density predictor.

Interpretable models to predict Breast Cancer

Several works in the literature use propositional (“black box”) approaches to generate prediction models. In this work we employ the Inductive Logic Programming technique, whose prediction model is based on first order rules, to the domain of breast cancer. These rules have the advantage of being interpretable and convenient to be used as a common language between the computer scientists and the medical experts. We also explore the relevance of some of variables usually collected to predict breast cancer. We compare our results with a propositional classifier that was considered best for the same dataset studied in this paper.

Knowledge on heart condition of children based on demographic and physiological features

We evaluated a population of 7199 children between 2 and 19 years old to study the relations between the observed demographic and physiological features in the occurrence of a pathological/non-pathological heart condition. The data was collected at the Real Hospital Português, Pernambuco, Brazil. We performed a feature importance study, with the aim of categorizing the most relevant variables, indicative of abnormalities. Results show that second heart sound, weight, heart rate, height and secondary reason for consultation are important features, but not nearly as decisive as the presence of heart murmurs. Quantitatively speaking, systolic murmurs and a hyperphonetic second heart sound increase the odds of having a pathology by a factor of 320 and 6, respectively.

Detecting cardiac pathologies from annotated auscultations

The DigiScope project aims at developing a digitally enhanced stethoscope capable of using state of the art technology in order to help physicians in their daily medical routine. One of the main tasks of DigiScope is to build a repository of auscultations (sound and medical related data). In this work, we present a preliminary analysis and study of the first auscultations performed on children of a Brazilian hospital. Results indicate that classifiers can be obtained that distinguish reasonably well patients with cardiac pathologies from those that do not have pathologies.

A Speech-to-Text Interface for MammoClass

Mammoclass is a web tool that allows users to enter a small set of variable values that describe a finding in a mammography, and produces a probability of this finding being malignant or benign. The tool requires that the user types in every variable a value in order to perform a prediction. In this work, we present a speech-to-text interface integrated to MammoClass that allows radiologists to speak up a mammography report instead of typing it in. This new MammoClass module can take audio content, transcribe it into written words, and automatically extract the variable values by applying a parser to the recognized text. Results of spoken mammography reports show that the same variables are extracted for both types of input: typed in or dictated text.