Sole-Search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data

Next-generation sequencing is revolutionizing the identification of transcription factor binding sites throughout the human genome. However, the bioinformatics analysis of large datasets collected using chromatin immunoprecipitation and high-throughput sequencing is often a roadblock that impedes researchers in their attempts to gain biological insights from their experiments. We have developed integrated peak-calling and analysis software (Sole-Search) which is available through a user-friendly interface and (i) converts raw data into a format for visualization on a genome browser, (ii) outputs ranked peak locations using a statistically based method that overcomes the significant problem of false positives, (iii) identifies the gene nearest to each peak, (iv) classifies the location of each peak relative to gene structure, (v) provides information such as the number of binding sites per chromosome and per gene and (vi) allows the user to determine overlap between two different experiments. In addition, the program performs an analysis of amplified and deleted regions of the input genome. This software is web-based and automated, allowing easy and immediate access to all investigators. We demonstrate the utility of our software by collecting, analyzing and comparing ChIP-seq data for six different human transcription factors/cell line combinations

Characterization of the Contradictory Chromatin Signatures at the 3′ Exons of Zinc Finger Genes

The H3K9me3 histone modification is often found at promoter regions, where it functions to repress transcription. However, we have previously shown that 3′ exons of zinc finger genes (ZNFs) are marked by high levels of H3K9me3. We have now further investigated this unusual location for H3K9me3 in ZNF genes. Neither bioinformatic nor experimental approaches support the hypothesis that the 3′ exons of ZNFs are promoters. We further characterized the histone modifications at the 3′ ZNF exons and found that these regions also contain H3K36me3, a mark of transcriptional elongation. A genome-wide analysis of ChIP-seq data revealed that ZNFs constitute the majority of genes that have high levels of both H3K9me3 and H3K36me3. These results suggested the possibility that the ZNF genes may be imprinted, with one allele transcribed and one allele repressed. To test the hypothesis that the contradictory modifications are due to imprinting, we used a SNP analysis of RNA-seq data to demonstrate that both alleles of certain ZNF genes having H3K9me3 and H3K36me3 are transcribed. We next analyzed isolated ZNF 3′ exons using stably integrated episomes. We found that although the H3K36me3 mark was lost when the 3′ ZNF exon was removed from its natural genomic location, the isolated ZNF 3′ exons retained the H3K9me3 mark. Thus, the H3K9me3 mark at ZNF 3′ exons does not impede transcription and it is regulated independently of the H3K36me3 mark. Finally, we demonstrate a strong relationship between the number of tandemly repeated domains in the 3′ exons and the H3K9me3 mark. We suggest that the H3K9me3 at ZNF 3′ exons may function to protect the genome from inappropriate recombination rather than to regulate transcription

Neuronal sensitivity to TDP-43 overexpression is dependent on timing of induction

Ubiquitin-immunoreactive neuronal inclusions composed of TAR DNA binding protein of 43 kDa (TDP-43) are a major pathological feature of frontotemporal lobar degeneration (FTLD-TDP). In vivo studies with TDP-43 knockout mice have suggested that TDP-43 plays a critical, although undefined role in development. In the current report, we generated transgenic mice that conditionally express wild-type human TDP-43 (hTDP-43) in the forebrain and established a paradigm to examine the sensitivity of neurons to TDP-43 overexpression at different developmental stages. Continuous TDP-43 expression during early neuronal development produced a complex phenotype, including aggregation of phospho-TDP-43, increased ubiquitin immunoreactivity, mitochondrial abnormalities, neurodegeneration and early lethality. In contrast, later induction of hTDP-43 in the forebrain of weaned mice prevented early death and mitochondrial abnormalities while yielding salient features of FTLD-TDP, including progressive neurodegeneration and ubiquitinated, phospho-TDP-43 neuronal cytoplasmic inclusions. These results suggest that neurons in the developing forebrain are extremely sensitive to TDP-43 overexpression and that timing of TDP-43 overexpression in transgenic mice must be considered when distinguishing normal roles of TDP-43, particularly as they relate to development, from its pathogenic role in FTLD-TDP and other TDP-43 proteinopathies. Finally, our adult induction of hTDP-43 strategy provides a mouse model that develops critical pathological features that are directly relevant for human TDP-43 proteinopathies

The calcareous brown alga Padina pavonica in southern Britain: population change and tenacity over 300 years

Understanding long-term persistence and variability in species populations can help to predict future survival, growth and distribution; however, sustained observations are exceedingly rare. We examine and interpret a remarkable record of the calcareous brown alga Padina pavonica (Phaeophyceae) at its northern limit on the south coast of England (50°N, 1–3°W) from 1680 to 2014, which is probably the longest compilation and review of any marine algal species. Over this period, which extends from the middle of the Little Ice Age to the present, there has been considerable variability in temperature and storminess. We identified a significant number of site extinctions in the second half of the nineteenth century, which coincided with cooler conditions and stormier weather. To interpret thesechanges, we measured recruitment, growth and production of tetraspores at sheltered and exposed sites in 2012–2014, years which had low and high spring temperatures. Potential spore production was greater at the sheltered site due to a longer growing period and survival of larger fronds. Delayed growth in the cooler spring resulted in smaller fronds and lower potential production of tetraspores by early summer. Yet in the warmer year, rapid initial growth caused higher sensitivity to damage and dislodgement by summer storms, which also limited potential spore production. Antagonistic responses to multiple stressors and disturbances make future predictions of survival and distribution difficult. Fronds of Padina pavonica are sensitive to both temperature and physical disturbances, yet vegetative perennation appears to have enabled population persistence and explained the longevity of remaining populations

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

Marine algal flora of São Miguel Island, Azores

Este artículo contiene 52 páginas, 4 tablas, 15 figuras.Background The macroalgal flora of the Island of São Miguel (eastern group of the Azores Archipelago) has attracted the interest of many researchers in the past, the first publications going back to the nineteenth century. Initial studies were mainly taxonomic, resulting in the publication of a checklist of the Azorean benthic marine algae. Later, the establishment of the University of the Azores on the Island permitted the logistic conditions to develop both temporal studies and long-term research and this resulted in a significant increase on research directed at the benthic marine algae and littoral communities of the Island and consequent publications. Prior to the present paper, the known macroalgal flora of São Miguel Island comprised around 260 species. Despite this richness, a significant amount of the research was never made public, notably Masters and PhD theses encompassing information regarding presence data recorded at littoral and sublittoral levels down to a depth of approximately 40 m around the Island and the many collections made, which resulted in vouchers deposited in the AZB Herbarium Ruy Telles Palhinha and the LSM- Molecular Systematics Laboratory at the Faculty of Sciences and Technology of the University of the Azores. The present publication lists the macroalgal taxonomic records, together with information on their ecology and occurrence around São Miguel Island, improving the knowledge of the Azorean macroalgal flora at local and regional scales. New information A total of 12,781 specimens (including some identified only to genus) belonging to 431 taxa of macroalgae are registered, comprising 284 Rhodophyta, 59 Chlorophyta and 88 Ochrophyta (Phaeophyceae). Of these, 323 were identified to species level (212 Rhodophyta, 48 Chlorophyta and 63 Ochrophyta), of which 61 are new records for the Island (42 Rhodophyta, 9 Chlorophyta and 10 Ochrophyta), one an Azorean endemic (Predaea feldmannii subsp. azorica Gabriel), five are Macaronesian endemisms (the red algae Botryocladia macaronesica Afonso-Carrillo, Sobrino, Tittley & Neto, Laurencia viridis Gil-Rodríguez & Haroun, Millerella tinerfensis (Seoane-Camba) S.M.Boo & J.M.Rico, Phyllophora gelidioides P.Crouan & H.Crouan ex Karsakoff and the green alga Codium elisabethiae O.C.Schmidt), 19 are introduced species (15 Rhodophyta, two Chlorophyta and two Ochrophyta) and 32 are of uncertain status (21 Rhodophyta, five Chlorophyta and six Ochrophyta).This research was supported by several projects, expeditions and campaigns (see Funding above) and lately by the project “ACORES-01-0145-FEDER-000072” funded the Operational Programme Azores 2020 (85% ERDF and 15% regional funds). Thanks are due to the campaign teams for their critical involvement in this project (Abel Sentíes, Aina del Alcázar, Ana Alfaya, Ana Belén Villalba Lapeña, Ana Santos, Ana Sofia Carreiro, André Amaral, Andrea Tracana, Ane Laborda, Anna Lloveras Armengol, António Brigos Plafon, Berta Solé Nadal, Camille Fontaine, Carlos Rius, Carles Mir, Caroline Terral, Catarina Santos, Cláudia Hipólito, Daniela Gabriel, Edward Hehre, Emanuel Xavier, Eduardo García, Enrique Almira, Esteban Belles, Eunice Nogueira, Fátima Vaz Pinto, Francisco Wallenstein, Gustavo M Martins, Heather Baldwin, Isadora Moniz, Jana Verdura, Joana Pombo, João Brum, João Faria Santos, João Ferreira, Laura Busquier, Marco Enoch, Maria Ana Dionísio, Maria Machín-Sánchez, Maria Vale, Marlene Terra, Mónica Martínez, Mutue Toyota Fujii, Patrícia Madeira, Pedro Raposeiro, Richard Fralick, Richard Thompson, Rocío Sánchez, Ruben Couto, Rubén Mosquera, Rui Sousa, Sara Peres, Tarso Costa, Tito Silva, Valeria Cassano, Virginie Leyendecker). Edgar Rosas Alquicira and Karla León Cisneros were supported by the Programme AlBan, the European Union Programme of High Level Scholarships for Latin America (through scholarships E05D060221MX and E05D060520MX), “Consejo Nacional de Ciencia y Tecnología” (doctoral scholarships 176162 and 157904) and the UNAMUNO Programme of PhD Scholarships for Europe. Eva Cacabelos was supported by a postdoctoral grant (Project M1420-09-5369-FSE-000002) from ARDITI (Regional Agency for Development of Research, Technology and Innovation of Madeira). Andrea Z. Botelho was supported by a PhD grant (M3.1.a/F/083/2015), awarded by Fundo Regional da Ciência e Tecnologia (FRCT). Afonso C.L. Prestes was supported by a PhD grant (M3.1.a/F/083/2015), awarded by Fundo Regional da Ciência e Tecnologia (FRCT). Rita F. Patarra was supported by a Science and Technology Management Fellowship grant (SFRH/BGCT/135478/2018), awarded by Fundação para a Ciência e a Tecnologia (FCT I.P.). Manuela I. Parente was supported by a Postdoc grant (SFRH/BPD/34246/2006), awarded by Fundação para a Ciência e a Tecnologia (FCT).Peer reviewe

Sole-Search: an integrated analysis program for peak detection and functional annotation using ChIP-seq data.

Next-generation sequencing is revolutionizing the identification of transcription factor binding sites throughout the human genome. However, the bioinformatics analysis of large datasets collected using chromatin immunoprecipitation and high-throughput sequencing is often a roadblock that impedes researchers in their attempts to gain biological insights from their experiments. We have developed integrated peak-calling and analysis software (Sole-Search) which is available through a user-friendly interface and (i) converts raw data into a format for visualization on a genome browser, (ii) outputs ranked peak locations using a statistically based method that overcomes the significant problem of false positives, (iii) identifies the gene nearest to each peak, (iv) classifies the location of each peak relative to gene structure, (v) provides information such as the number of binding sites per chromosome and per gene and (vi) allows the user to determine overlap between two different experiments. In addition, the program performs an analysis of amplified and deleted regions of the input genome. This software is web-based and automated, allowing easy and immediate access to all investigators. We demonstrate the utility of our software by collecting, analyzing and comparing ChIP-seq data for six different human transcription factors/cell line combinations

Benthic communities of the bay of São Vicente (São Miguel, Azores).

34th European Marine Biology Symposium. Ponta Delgada, Açores, 13-17 de Setembro de 1999

Marine algal flora of Flores and Corvo Islands, Azores

BACKGROUND The algal flora of the western group of the Azores archipelago (Islands of Flores and Corvo) has attracted the interest of many researchers on numerous past occasions (such as Drouet 1866, Trelease 1897, Gain 1914, Schmidt 1929, Schmidt 1931, Azevedo et al. 1990, Fralick and Hehre 1990, Neto and Azevedo 1990, Neto and Baldwin 1990, Neto 1996, Neto 1997, Neto 1999, Tittley and Neto 1996, Tittley and Neto 2000, Tittley and Neto 2005, Tittley and Neto 2006, Azevedo 1998, Azevedo 1999, Tittley et al. 1998, Dionísio et al. 2008, Neto et al. 2008). Despite this interest, the macroalgal flora of the Islands cannot be described as well-known with the published information reflecting limited collections preformed in short-term visits by scientists. To overcome this, a thorough investigation, encompassing collections and presence data recording, has been undertaken for both the littoral and sublittoral regions, down to a depth of approximately 40 m, covering a relatively large area on both Islands (approximately 143 km² for Flores and 17 km² for Corvo). This paper lists the resultant taxonomic records and provides information on species ecology and occurrence around both these Islands, thereby improving the knowledge of the Azorean macroalgal flora at both local and regional scales. NEW INFORMATION For the Island of Flores, a total of 1687 specimens (including some taxa identified only to genus level) belonging to 196 taxa of macroalgae are registered, comprising 120 Rhodophyta, 35 Chlorophyta and 41 Ochrophyta (Phaeophyceae). Of these taxa, 128 were identified to species level (80 Rhodophyta, 22 Chlorophyta and 26 Ochrophyta), encompassing 37 new records for the Island (20 Rhodophyta, 6 Chlorophyta and 11 Ochrophyta); two Macaronesian endemics (Laurencia viridis Gil-Rodríguez & Haroun and Millerella tinerfensis (Seoane-Camba) S.M.Boo & J.M.Rico); six introduced (the Rhodophyta Asparagopsis armata Harvey, Neoizziella divaricata (C.K.Tseng) S.-M.Lin, S.-Y.Yang & Huisman and Symphyocladia marchantioides (Harvey) Falkenberg; the Chlorophyta Codium fragile subsp. fragile (Suringar) Hariot; and the Ochrophyta Hydroclathrus tilesii (Endlicher) Santiañez & M.J.Wynne and Papenfussiella kuromo (Yendo) Inagaki); and 14 species of uncertain status (10 Rhodophyta, two Chlorophyta and two Ochrophyta). For the Island of Corvo, a total of 390 specimens distributed in 56 taxa of macroalgae are registered, comprising 30 Rhodophyta, nine Chlorophyta and 17 Ochrophyta (Phaeophyceae). Whilst a number of taxa were identified only to the genus level, 43 were identified to species level (22 Rhodophyta, eight Chlorophyta and 13 Ochrophyta), comprising 22 new records for the Island (nine Rhodophyta, four Chlorophyta and nine Ochrophyta), two introduced species (the Rhodophyta Asparagopsis armata and the Chlorophyta Codium fragile subsp. fragile and seven species of uncertain status (five Rhodophyta and two Ochrophyta).This paper is the result of several projects, expeditions and campaigns (see Funding above) and is supported by the project “ACORES-01-0145-FEDER-000072” as part of the Operational Programme Azores 2020 (85% ERDF and 15% regional funds). Manuela I. Parente was supported by a Postdoc grant (SFRH/BPD/34246/2006) awarded by Fundação para a Ciência e a Tecnologia (FCT). Afonso Prestes was supported by a PhD grant (M3.1.a/F/083/2015) awarded by Fundo Regional da Ciência e Tecnologia (FRCT). WF was awarded grants from the British Council and Earthwatch.info:eu-repo/semantics/publishedVersio