Analysis of the contribution of alternative splicing to glioma subtype definition

Tese de mestrado em Bioinformática e Biologia Computacional, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016Gliomas são tumores cerebrais que têm origem em dois tipos de células: os astrócitos e os ologodendrócitos, os quais formam uma estrutura de suporte para os neurónios. Os gliomas são responsáveis por cerca de 80 % dos casos malignos de tumor cerebral. A classificação de gliomas fundou-se durante muito tempo em parâmetros histológicos, tais como o tipo histológico ou o estádio do tumor, uma medida do seu grau de malignidade, baseada na aparência e comportamento das células. A realização de estudos de larga escala fazendo uso das novas tecnologias ómicas, tem permitido melhorar os sistemas de classificação clássicos, através da identificação de assinaturas moleculares subjacentes aos diferentes subtipos tumorais. No caso de gliomas, uma publicação recente fez a descrição de um sistema de classificação robusto, baseado num painel de 1300 marcadores de metilação de DNA, aplicável a tumores dos estádios de 2 a 4, em que são definidos seis subtipos (LGm1 a LGm6) que formam grupos prognóstico bastante homogéneos (Ceccarelli et al., 2016). O splicing é um mecanismo de processamento pós-transcricional através do qual certos segmentos de uma molécula de pre-RNA mensageiro (pre-mRNA): os intrões, são eliminados, resultando num mRNA maduro constituído por segmentos chamados exões que codifica para uma proteína (ou produto génico). É um processo químico levado a cabo por um complexo macromolecular modular, que se designa por spliceossoma. O splicing alternativo consiste na produção de mais do que um tipo de mRNA maduro a partir do mesmo gene através da retenção ou eliminação seletiva de um exão/intrão, dito alternativo ou regulado. Este processo contribui para a geração de diversidade funcional de produtos génicos e é regulado de forma específica em cada tecido e estádio de desenvolvimento, sendo que alterações aos seus padrões normais estão descritos como podendo promover ou apoiar o processo de tumorigénese. A quantificação de splicing alternativo pode ser feita usando uma medida que se designa por index da percentagem de splicing ou PSI, e que corresponde à proporção de transcritos que incluem um exão regulado em relação ao total de transcritos de um gene. O presente projeto de tese visa analisar a contribuição da regulação de splicing alternativo para a definição da classificação dos gliomas de estádios 2 a 4, tendo como objeto de estudo o conjunto de dados de uma coorte de 674 casos de glioma depositado no portal TCGA (The Cancer Genome Atlas). Por forma a avaliar a existência de uma assinatura molecular própria ou associada aos subtipos de glioma estabelecidos, utilizou-se análise multivariada dos dados de quantificação de splicing alternativo, mas também de expressão génica. Utilizando análise de componentes principais (PCA), o splicing alternativo mostrou capturar diversidade biológica de forma muito semelhante à expressão génica. A componente principal associada aos dois níveis de dados transcriptómicos de maior relevância representou um gradiente de malignidade tumoral. O splicing alternativo demonstrou ser informativo relativamente à distinção dos subtipos LGm2, LGm3 e LGm4/5, enquanto os subtipos LGm1 e LGm6 revelaram uma grande heterogeneidade. Análise de expressão génica e splicing alternativo diferencial ao longo dos subtipos LGm permitiu identificar um grupo de 5970 genes e 1762 eventos de splicing associados à definição desses subtipos. De forma importante, 183 genes e 105 eventos de splicing com regulação diferencial afetam genes cujas mutações têm implicação causal em cancro demonstrada. Por fim, 41 fatores de splicing apresentaram de igual modo expressão génica diferencial entre subtipos, com os genes IGF2BP2 e IGF2BP3 apresentando os resultados mais significativos, nomeadamente uma expressão elevada em LGm1,4,5 e 6, os subtipos associado a um pior prognóstico. Análise de enriquecimento funcional realizada com a informação de regulação diferencial da expressão génica e splicing alternativo entre subtipos LGm revelou funções bilógicas distintas por cada processo. Enquanto os genes com alterações de expressão entre grupos de metilação de DNA se relacionaram com funções como resposta imune, proliferação, sobrevivência e adesão celulares, genes tendo o seu splicing alternativo alterado involveram sobretudo o processamento de RNA, síntese proteica e também apoptose. O valor do splicing alternativo e da expressão génica para o prognóstico em gliomas foi avaliado usado modelos de regressão de Cox para a sobrevida do paciente em função de diferentes fatores de risco. Um teste inicial sobre a capacidade da componente principal associada à malignidade para explicar a evolução do tempo de sobrevida do doente confirmou a superioridade desta dimensão dos dados de transcriptómica relativamente à variável estádio do tumor no que diz respeito a essa previsão. Subsequente análise de eventos de splicing e genes individuais como preditores de prognóstico resultou na descoberta de tantos quantos 11794 genes e 6657 eventos de splicing. Porém, apenas um gene e dois eventos de splicing alternativo foram capazes de melhorar a estimativa da evolução do doente relativamente a um modelo já contendo subtipos LGm, estádio do tumor e idade do doente, três covariáveis relevantes descritas na literatura. Os dois eventos em questão apresentaram distribuições de PSIs com variãncia muito baixa, pelo que constituiriam marcadores de prognóstico de pouca qualidade, além de não parecerem ter um interesse intrínseco já que não representam a possibilidade de geração de uma transição de uma isoforma dominante para outra. Finalmente, marcadores especificamente associados aos grupos LGm foram identificados a partir da interseção do conjunto que apresentou valor prognóstico independente do estádio do tumor e da idade do doente com o conjunto com regulação diferencial entre os seis subtipos. Desta análise resultou um total de 337 eventos de splicing alternativo, 50 dos quais acrescentando informação prognóstica relativamente aos dados de expressão génica, e também 20 genes de fatores de splicing. De entre estes últimos, seis codificavam para proteínas que se ligam ao RNA (RBPs) com motivos de ligação conhecidos, pelo que o seu potencial papel regulatório foi investigado. Uma metodologia para a descoberta de mecanismos de regulação de splicing alternativo em trans foi implementada. Concretamente, um algoritmo para a geração de mapas de regulação de splicing específicos de cada RBP foi usado, tendo como objetivo determinar as regiões regulatórias para fomento ou silenciamento do splicing de exões alternativos. A identificação da posição relativa dos alvos de regulação de cada RBP baseou-se na deteção dos eventos de splicing cujas percentagens de inclusão do exão alternativo se correlacionavam com a abundância da RBP e que efetivamente continham motivos de ligação para essa RBP nas regiões vizinhas do exão regulado. Este método foi validado para o fator de splicing bem estudado PTBP1, utilizando tanto um conjunto de dados provindo de tecidos saudáveis como com o da cohorte de glioma estudada. No entanto, a aplicação do mesmo procedimento a quatro dos seis fatores de splicing potencialmente associados com as alterações de splicing entre subtipos de glioma resultou em mapas de splicing de RNA inconsistentes entre os dois conjuntos de dados. Medidas para a melhoria desta metodologia foram identificadas e poderão ser aplicadas futuramente por forma a poder concluir sobre a relevância destas proteínas em glioma. Este estudo permitiu identificar um número de eventos de splicing alternativo e genes expressos, nomeadamente, genes de fatores de splicing, que apresentam comportamento diferencial em termos de malignidade e subtipo epigenático de glioma e que poderão ter valor diagnóstico e terapêutico interessante. Adicionalmente, um novo método computacional para descoberta de mecanismos de regulação de splicing alternativo foi implementado, tendo permitido propor um mecanismo de ação para o fator de splicing relevante em glioma KHDRBS2.Gliomas are brain primary tumours that originate from two kinds of glial cells: astrocytes and oligodendrocytes, which make up a supportive structure for neurons. Classification of gliomas has for long relied on histological parameters, like cell type composition and grade, a measurement of the degree of malignancy of a tumour based on cell appearance and behaviour. Large scale studies employing the new omics technologies have allowed to improve classic classification systems, through the identification of molecular signatures behind each tumour subtype. In the case of gliomas, a recent publication described a robust classification system based on DNA-methylation profiling, applicable to tumours from grades 2 to 4 and defining six subtypes (LGm1 to LGm6) forming quite homogeneous prognostic groups (Ceccarelli et al., 2016). Alternative splicing is a post-transcriptional mechanism of regulation of gene expression that contributes to generate functional diversity of gene products through the selective elimination of certain segments of pre-messenger RNA (pre-mRNA) molecules. Alternative splicing is regulated in a tissue and developmental specific way and alterations to its normal patterns have been extensively reported to promote or help sustaining tumorigenesis. The work presented here aimed at determining the contribution of alternative splicing to glioma subtype definition, having as a focus a cohort of 674 cases of glioma grades 2 to 4, coming from the Cancer Genome Atlas (TCGA) data portal. Differential gene expression and differential splicing analyses across LGm subtypes allowed to identify a group of 5970 genes and 1762 events of alternative splicing whose regulation is associated with subtype definition. Importantly, among these differentially regulated markers, there were 41 splicing factor genes and 46 splicing factor gene-associated events of splicing. In order to enquire about the existence of particular molecular signatures in glioma, multivariate exploratory data analysis was performed on alternative splicing and also gene expression data. Alternative splicing showed to capture sample diversity in a way that was very similar to gene expression. The most revealing principal component associated with both transcriptomic data levels presented a gradient of tumour malignancy. As for the ability of alternative splicing to distinguish subtypes, it could partially separate LGm2, LGm3 and LGm4/5 groups, while LGm1 and LGm6 revealed a high heterogeneity. The value of alternative splicing and gene expression in glioma prognosis was evaluated using Cox regression models for patient’s overall survival outcome as a function of different predictors. An initial test on the ability of the malignancy associated principle component to explain patient outcome strikingly confirmed the superiority of this dimension of transcriptomic data to make this prediction in relation to tumour grade. In turn, analysis of individual alternative splicing events and expressed genes as prognosis predictors resulted in as many as 11794 genes and 6657 events of splicing. However, only one gene and two alternative splicing events were able to improve patient survival outcome estimation relative to a model that already accounted for LGm subtype, tumour grade and patient age, three relevant covariates described in the literature. Finally, in terms of prognostic markers specifically associated with LGm groups, a total of 337 splicing events were found, 50 of which adding information in relation to gene expression, and also 20 splicing factor genes. From these latter, six encoded RNA-binding proteins (RBPs) with known RNA-binding motifs and their potential regulatory role was investigated. A methodology for the discovery of mechanisms of alternative splicing regulation in trans was implemented. Specifically, an algorithm to generate maps of splicing regulation specific of each RBP was used, aimed at determining regulatory regions for their enhancing or silencing role in splicing of alternative exons. This method was validated for the known splicing factor PTBP1, both using an RNA-seq dataset from healthy tissues and the studied glioma one. However, application of the same procedure to four of the six splicing factors potentially associated with alternative splicing changes across glioma subtypes resulted in RNA splicing maps that were inconsistent between the two datasets. Improvements to the methodology used were identified and may be applied in the future so that stronger conclusions about the relevance of these proteins in glioma can be taken. This study allowed to outline a number of alternative splicing events and expressed genes, namely splicing factor genes, that behave differently according to glioma malignancy and epigenetic groups and that may be of interesting diagnostic and therapeutic value. Also, a novel computational method for discovery of mechanisms of regulation of alternative splicing was implemented and allowed to proposal a mechanism of action for the glioma-relevant splicing factor KHDRBS2

Educação para uma cidadania crítica, global e criativa: um olhar com perspetiva de género

Vivemos num mundo em constante mudança e num tempo em que coexistem vários problemas globais. Se, atualmente, o acesso à educação e à informação possibilita, a um maior número de pessoas, o conhecimento, mais oportunidades e a reivindicação dos seus direitos enquanto cidadãs, por outro lado, os contextos sociais, ambientais e políticas/os em que vivemos, a par da iliteracia digital e mediática têm constituído uma ameaça às conquistas realizadas em matéria de direitos humanos e, mais concretamente, de igualdade de género. A Escola é o local privilegiado para as crianças e jovens construírem uma cidadania crítica, global e criativa. A cidadania implica um processo educativo contínuo e, por isso, deve ser desenvolvida de modo explícito. Enquanto protagonistas no processo de ensino-aprendizagem, as suas aprendizagens serão tanto mais significativas, quanto mais este processo ocorrer a partir das suas experiências, questionamentos e reflexões críticas. As crianças e jovens necessitam de um currículo escolar para a cidadania, de modo a terem oportunidade de falar e refletir sobre temas importantes para elas/eles e que as/os capacitem e impliquem numa mudança coletiva necessária para os problemas globais com que a sociedade depara. Neste artigo, apresenta-se o Programa de Prevenção Primária da violência de género da UMAR que tem vindo a ser implementado em contexto escolar pelo ART’THEMIS+, sob uma perspectiva de género, com técnicas/os/profissionais especializadas/os. Este projeto em parceria com a comunidade educativa, desenvolve um trabalho pedagógico colaborativo para a construção de uma sociedade sem violência.info:eu-repo/semantics/publishedVersio

A genetically modified Plasmodium berghei parasite as a surrogate for whole-sporozoite vaccination against P. vivax malaria

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Two malaria parasite species, Plasmodium falciparum (Pf) and P. vivax (Pv) are responsible for most of the disease burden caused by malaria. Vaccine development against this disease has focused mainly on Pf. Whole-sporozoite (WSp) vaccination, targeting pre-erythrocytic (PE) parasite stages, is a promising strategy for immunization against malaria and several PfWSp-based vaccine candidates are currently undergoing clinical evaluation. In contrast, no WSp candidates have been developed for Pv, mainly due to constraints in the production of Pv sporozoites in the laboratory. Recently, we developed a novel approach for WSp vaccination against Pf based on the use of transgenic rodent P. berghei (Pb) sporozoites expressing immunogens of this human-infective parasite. We showed that this platform can be used to deliver PE Pf antigens, eliciting both targeted humoral responses and cross-species cellular immune responses against Pf. Here we explored this WSp platform for the delivery of Pv antigens. As the Pv circumsporozoite protein (CSP) is a leading vaccine candidate antigen, we generated a transgenic Pb parasite, PbviVac, that, in addition to its endogenous PbCSP, expresses PvCSP under the control of a strictly PE promoter. Immunofluorescence microscopy analyses confirmed that both the PbCSP and the PvCSP antigens are expressed in PbviVac sporozoites and liver stages and that PbviVac sporozoite infectivity of hepatic cells is similar to that of its wild-type Pb counterpart. Immunization of mice with PbviVac sporozoites elicits the production of anti-PvCSP antibodies that efficiently recognize and bind to Pv sporozoites. Our results warrant further development and evaluation of PbviVac as a surrogate for WSp vaccination against Pv malaria.A.D. and J.C.S. were supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (U19AI110820 and R01AI141900). A.M.M. acknowledges Fundação para a Ciência e Tecnologia, Portugal (FCT) for Grant PTDC-BBB-BMD-2695-2014. M.P. acknowledges the “la Caixa” Foundation for Grant HR21-848, the GSK OpenLab Foundation for grant TC269, and FCT for grant PTDC-SAU-INF-29550-2017. D.M. acknowledges FCT for grant SFRH/BD/144817/2019.info:eu-repo/semantics/publishedVersio

EVIDÊNCIAS DE CONSTRUCTO Y INVARIANCIA FACTORIAL DE LA ESCALA DE ENCAJAMIENTO EN EL TRABAJO EN DISTINTAS ORGANIZACIONES EN EL BRASIL

Na psicologia das organizações e do trabalho, o construto do engajamento no trabalho é compreendido como um estado psicológico ativo que relaciona as emoções como determinantes da satisfação e do prazer do trabalhador na dinâmica organizacional, conduzindo ao envolvimento e dedicação deste. No Brasil, poucos estudos vêm se preocupando com a verificação da qualidade e manutenção de uma medida de engajamento no trabalho em termos temporais. O presente estudo tem como objetivo avaliar a consistência e invariância da estrutura fatorial da escala de engajamento no trabalho. 569 trabalhadores distribuído em duas amostras distintas, com idades acima de 18 anos, 62 % do sexo feminino, 63% de empresa pública e renda econômica acima de 2.000,00 reais, responderam, através de um link enviado para o e-mail pessoal ou rede social, a escala de engajamento no trabalho e dados sociodemográficos. Observaram-se que, na análise exploratória e confirmatória, os indicadores psicométricos garantiram a consistência e invariância da estrutura bi-fatorial da medida de engajamento para o contexto organizacional. Essa escala não apenas corrobora a capacidade de avaliação do construto, mas também a perspectiva teórica abordada com trabalhadores, contribuindo para a auto-avaliação do papel profissional e a função organizacional do trabalhador na gestão de pessoas.In the psychology of organizations and work, the work engagement construct is been understood as an active psychological state that relates emotions as determinants of worker satisfaction and pleasure in organizational dynamics, leading to the involvement and dedication of the worker. In  Brazil, few studies have been worrying about the verification of quality and maintenance of a measure of work engagement in temporal terms. The present study evaluates the consistency and invariance of the factorial structure of the work engagement scale. 569 workers distributed in two distinct samples, aged over 18 years, 62% female, 63% from public companies and economic income above 2,000.00 reais, answered through a link sent to the personal e-mail or their social network the scale of work engagement and sociodemographic data. It was observed that, in the exploratory and confirmatory analysis, the psychometric indicators guaranteed the consistency and invariance of the bi-factorial structure of the measure of engagement for the organizational context. This scale not only corroborates the assessment capacity of the construct, but also the theoretical perspective approached with workers, contributing to the self-evaluation of the professional role and the organizational function of the worker in the management of people.En la psicología de las organizaciones y del trabajo, el constructo del encajamiento en el trabajo es comprendido como un período psicológico activo que relaciona las emociones como distintivas de la satisfacción y del placer del trabajador en la dinámica organizacional, conduciendo al envolvimiento y dedicación de este. En el Brasil, pocos estudios hacen preocupación con la verificación de la cualidad y manutención de una medida de encajamiento en el trabajo en términos temporales; la presente investigación tiene como objetivo evaluar la consistencia e invariancia de la estructura factorial de la escala de encajamiento en el trabajo. 569 trabajadores, distribuidos en dos amuestras distintas, con edades a cima de 18 años, 62% del género femenino, 63% de empresa pública y renta económica a cima de R$ 2.000,00 reales, respondieron a través de un link enviado para el correo electrónico personal o red social, la escala de encajamiento en el trabajo y datos sociodemográficos. Observase que, en el análisis exploratoria y confirmatoria, los indicadores psicométricos garantieran la consistencia e invariancia de la estructura bi-factorial de la medida de encajamiento para el contexto organizacional. Esta escala no solo corrobora a la capacidad de evaluación del constructo, pero también, la perspectiva teórica abordada con trabajadores, contribuyendo para la autoevaluación sobre el papel profesional y la función organizacional del trabajador en la gestión de personas

Association of the clinical profile and overall survival of pediatric patients with acute lymphoblastic leukemia

IntroductionThe clarification of etiopathology, the improvement of chemotherapy regimens and their risk stratifications, and the improvement in treatment support have increased the survival of children and adolescents affected by Acute Lymphoblastic Leukemia (ALL) past few years. This study aimed to estimate overall survival (OS) and event-free survival (EFS) in an onco-hematology treatment center in Brazil, reports the main clinical-laboratory characteristics of patients at diagnosis, verify the frequency of treatment-related adverse effects and the main causes of death.Material and methodsRetrospective analysis involving patients diagnosed with ALL, treated with the protocol of the Brazilian Group for Treatment of Leukemias in Childhood (GBTLI), between 2010 and 2020 was carried out; the outcomes (relapse, deaths, development of new neoplasms) were analyzed SPSS® software was used for the statistical analyses, and the p-value was considered significant when less than 0.05 for all analyses.Results109 patients were included in the study; the median age was 5 years, with a slight predominance of males. Sixty-six patients were classified as high-risk (HR) group and 43 patients were classified as low-risk (LR) group. After 5 years of diagnosis, the OS was 71.5%, and the EFS was 65%. No statistical difference was found between the HR and LR groups for OS and EFS, while leukocyte counts were statistically associated with the outcome of death (p = 0.028). Among the patients, 28 (25.6%) died due to infection accounting 46.4% of death causes. Among the 34 patients with unfavorable outcomes (death and/or relapse), 32 had no research for the minimal residual disease at the end of remission induction, and 25 were not investigated for the presence of chromosomal abnormalities. The most reported complications and treatment-related adverse effects were increased liver transaminases (85.9%), airway infection (79.4%), oral mucositis (67.2%), febrile neutropenia (64.4%), and diarrhea (36.4%).ConclusionsThe rates of OS and EFS obtained in this cohort are similar to those obtained in the few previous similar studies in Brazil and lower than those carried out in developed countries. The unavailability of prognostic tests may have hindered risk stratification and influenced the results obtained

Identification of clusters of asthma control: A preliminary analysis of the inspirers studies

This work was funded by ERDF (European Regional Development Fund) through the operations: POCI- -01-0145-FEDER-029130 (“mINSPIRERS—mHealth to measure and improve adherence to medication in chronic obstructive respiratory diseases - generalisation and evaluation of gamification, peer support and advanced image processing technologies”) co-funded by the COMPETE2020 (Programa Operacional Competitividade e Internacionalização), Portugal 2020 and by Portuguese Funds through FCT (Fundação para a Ciência e a Tecnologia).© 2020, Sociedade Portuguesa de Alergologia e Imunologia Clinica. All rights reserved. Aims: To identify distinct asthma control clusters based on Control of Allergic Rhinitis and Asthma Test (CARAT) and to compare patients’ characteristics among these clusters. Methods: Adults and adolescents (≥13 years) with persistent asthma were recruited at 29 Portuguese hospital outpatient clinics, in the context of two observational studies of the INSPIRERS project. Demographic and clinical characteristics, adherence to inhaled medication, beliefs about inhaled medication, anxiety and depression, quality of life, and asthma control (CARAT, >24 good control) were collected. Hierarchical cluster analysis was performed using CARAT total score (CARAT-T). Results: 410 patients (68% adults), with a median (percentile 25–percentile 75) age of 28 (16-46) years, were analysed. Three clusters were identified [mean CARAT-T (min-max)]: cluster 1 [27(24-30)], cluster 2 [19(14-23)] and cluster 3 [10(2-13)]. Patients in cluster 1 (34%) were characterised by better asthma control, better quality of life, higher inhaler adherence and use of a single inhaler. Patients in clusters 2 (50%) and 3 (16%) had uncontrolled asthma, lower inhaler adherence, more symptoms of anxiety and depression and more than half had at least one exacerbation in the previous year. Further-more, patients in cluster 3 were predominantly female, had more unscheduled medical visits and more anxiety symp-toms, perceived a higher necessity of their prescribed inhalers but also higher levels of concern about taking these inhalers. There were no differences in age, body mass index, lung function, smoking status, hospital admissions or specialist physician follow-up time among the three clusters. Conclusion: An unsupervised method based on CARAT--T, identified 3 clusters of patients with distinct, clinically meaningful characteristics. The cluster with better asthma control had a cut-off similar to the established in the validation study of CARAT and an additional cut-off seems to distinguish more severe disease. Further research is necessary to validate the asthma control clusters identified.publishersversionpublishe

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost