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Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: a Feature Selection Approach
International Journal of Molecular Sciences Article Long Non-Coding RNA Landscape in Prostate Cancer Molecular Subtypes: A Feature Selection Approach Simona De Summa 1,* , Antonio Palazzo 2 , Mariapia Caputo 1, Rosa Maria Iacobazzi 3 , Brunella Pilato 1, Letizia Porcelli 3, Stefania Tommasi 1 , Angelo Virgilio Paradiso 4,† and Amalia Azzariti 3,† 1 Molecular Diagnostics and Pharmacogenetics Unit, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] (M.C.); [email protected] (B.P.); [email protected] (S.T.) 2 Laboratory of Nanotechnology, IRCCS IstitutoTumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] 3 Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] (R.M.I.); [email protected] (L.P.); [email protected] (A.A.) 4 Scientific Directorate, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy; [email protected] * Correspondence: [email protected] † Co-senior authors. Abstract: Prostate cancer is one of the most common malignancies in men. It is characterized by a high molecular genomic heterogeneity and, thus, molecular subtypes, that, to date, have not been used in clinical practice. In the present paper, we aimed to better stratify prostate cancer patients through the selection of robust long non-coding RNAs. To fulfill the purpose of the study, a bioinformatic approach focused on feature selection applied to a TCGA dataset was used. In such a way, LINC00668 and long non-coding(lnc)-SAYSD1-1, able to discriminate ERG/not-ERG subtypes, Citation: De Summa, S.; Palazzo, A.; were demonstrated to be positive prognostic biomarkers in ERG-positive patients. -
A Genomics Approach Reveals Insights Into the Importance of Gene Losses for Mammalian Adaptations
Corrected: Publisher correction ARTICLE DOI: 10.1038/s41467-018-03667-1 OPEN A genomics approach reveals insights into the importance of gene losses for mammalian adaptations Virag Sharma1,2,3, Nikolai Hecker1,2,3, Juliana G. Roscito1,2,3, Leo Foerster1,2,3, Bjoern E. Langer1,2,3 & Michael Hiller1,2,3 1234567890():,; Identifying the genomic changes that underlie phenotypic adaptations is a key challenge in evolutionary biology and genomics. Loss of protein-coding genes is one type of genomic change with the potential to affect phenotypic evolution. Here, we develop a genomics approach to accurately detect gene losses and investigate their importance for adaptive evolution in mammals. We discover a number of gene losses that likely contributed to morphological, physiological, and metabolic adaptations in aquatic and flying mammals. These gene losses shed light on possible molecular and cellular mechanisms that underlie these adaptive phenotypes. In addition, we show that gene loss events that occur as a consequence of relaxed selection following adaptation provide novel insights into species’ biology. Our results suggest that gene loss is an evolutionary mechanism for adaptation that may be more widespread than previously anticipated. Hence, investigating gene losses has great potential to reveal the genomic basis underlying macroevolutionary changes. 1 Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden, Germany. 2 Max Planck Institute for the Physics of Complex Systems, Noethnitzer Str. 38, 01187 Dresden, Germany. 3 Center for Systems Biology Dresden, Pfotenhauerstr. 108, 01307 Dresden, Germany. Correspondence and requests for materials should be addressed to M.H. (email: [email protected]) NATURE COMMUNICATIONS | (2018) 9:1215 | DOI: 10.1038/s41467-018-03667-1 | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | DOI: 10.1038/s41467-018-03667-1 ne of the most fascinating aspects of nature is the a b % conserved genes diversity of life. -
Array Painting Reveals a High Frequency of Balanced Translocations in Breast Cancer Cell Lines That Break in Cancer-Relevant Genes
Oncogene (2008) 27, 3345–3359 & 2008 Nature Publishing Group All rights reserved 0950-9232/08 $30.00 www.nature.com/onc ONCOGENOMICS Array painting reveals a high frequency of balanced translocations in breast cancer cell lines that break in cancer-relevant genes KD Howarth1, KA Blood1,BLNg2, JC Beavis1, Y Chua1, SL Cooke1, S Raby1, K Ichimura3, VP Collins3, NP Carter2 and PAW Edwards1 1Department of Pathology, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK; 2Wellcome Trust Sanger Institute, Cambridge, UK and 3Department of Pathology, Division of Molecular Histopathology, Addenbrookes Hospital, University of Cambridge, Cambridge, UK Chromosome translocations in the common epithelial tion and inversion, which can result in gene fusion, cancers are abundant, yet little is known about them. promoter insertion or gene inactivation. As is well They have been thought to be almost all unbalanced and known in haematopoietic tumours and sarcomas, therefore dismissed as mostly mediating tumour suppres- translocations and inversions can have powerful onco- sor loss. We present a comprehensive analysis by array genic effects on specific genes and play a central role in painting of the chromosome translocations of breast cancer development (Rowley, 1998). In the past there cancer cell lines HCC1806, HCC1187 and ZR-75-30. In has been an implicit assumption that such rearrange- array painting, chromosomes are isolated by flow ments are not significant players in the common cytometry, amplified and hybridized to DNA microarrays. epithelial -
Supplementary Information
Supplementary Information A genomics approach reveals insights into the importance of gene losses for mammalian adaptations Sharma et al. The Supplementary Information contains - Supplementary Figures 1 - 35 - Supplementary Tables 1 - 8 - Supplementary Notes 1 - 8 1 A reference species with B annotated functional genes ? ? ? ? ? ? use Dollo parsimony ? ? to infer gene ancestry ? search for gene losses reference ? in query species ? ? ? ? ? non-ancestral branches Supplementary Figure 1: General framework for detecting gene losses in genome alignments. (A) Our approach considers all coding genes that are annotated and thus likely functional in a chosen reference species. We detect loss of a given gene in other query species by searching genome alignments for gene-inactivating mutations. Genome alignments are well-suited to detect gene losses for the following reasons. First, genome alignments can reveal the remnants of inactivated but not completely deleted genes, even if these genes are not expressed anymore and thus are not contained in a transcriptome or in mRNA/protein databases. Second, splice site mutations, which are one important class of inactivating mutations, can only be detected at the genomic but not at the mRNA/protein level. Third, information about missing sequence (assembly gaps, regions of low sequencing quality) are only visible by direct genome analysis. This is important as the absence of a gene in a gene/protein database or in a genomic BLAST run cannot distinguish between artifacts that perfectly mimic absence of a gene (such as large assembly gaps) and the complete deletion of a gene. Since gene loss in a query species requires that the common ancestor of the reference and this query species possessed the gene, we used Dollo parsimony to infer gene ancestry based on query species where the gene lacks any gene-inactivating mutations. -
Detection of H3k4me3 Identifies Neurohiv Signatures, Genomic
viruses Article Detection of H3K4me3 Identifies NeuroHIV Signatures, Genomic Effects of Methamphetamine and Addiction Pathways in Postmortem HIV+ Brain Specimens that Are Not Amenable to Transcriptome Analysis Liana Basova 1, Alexander Lindsey 1, Anne Marie McGovern 1, Ronald J. Ellis 2 and Maria Cecilia Garibaldi Marcondes 1,* 1 San Diego Biomedical Research Institute, San Diego, CA 92121, USA; [email protected] (L.B.); [email protected] (A.L.); [email protected] (A.M.M.) 2 Departments of Neurosciences and Psychiatry, University of California San Diego, San Diego, CA 92103, USA; [email protected] * Correspondence: [email protected] Abstract: Human postmortem specimens are extremely valuable resources for investigating trans- lational hypotheses. Tissue repositories collect clinically assessed specimens from people with and without HIV, including age, viral load, treatments, substance use patterns and cognitive functions. One challenge is the limited number of specimens suitable for transcriptional studies, mainly due to poor RNA quality resulting from long postmortem intervals. We hypothesized that epigenomic Citation: Basova, L.; Lindsey, A.; signatures would be more stable than RNA for assessing global changes associated with outcomes McGovern, A.M.; Ellis, R.J.; of interest. We found that H3K27Ac or RNA Polymerase (Pol) were not consistently detected by Marcondes, M.C.G. Detection of H3K4me3 Identifies NeuroHIV Chromatin Immunoprecipitation (ChIP), while the enhancer H3K4me3 histone modification was Signatures, Genomic Effects of abundant and stable up to the 72 h postmortem. We tested our ability to use H3K4me3 in human Methamphetamine and Addiction prefrontal cortex from HIV+ individuals meeting criteria for methamphetamine use disorder or not Pathways in Postmortem HIV+ Brain (Meth +/−) which exhibited poor RNA quality and were not suitable for transcriptional profiling. -
Genomic Landscape of Human Allele-Specific DNA Methylation
Genomic landscape of human allele-specific DNA methylation Fang Fanga, Emily Hodgesb, Antoine Molarob, Matthew Deana, Gregory J. Hannonb, and Andrew D. Smitha,1 aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California; and bHoward Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724 Edited by Wing Hung Wong, Stanford University, Stanford, CA, and approved March 8, 2012 (received for review January 24, 2012) DNA methylation mediates imprinted gene expression by passing stages preceding the context in which they become active. Such an epigenomic state across generations and differentially marking methods have been successfully applied to identify unique im- specific regulatory regions on maternal and paternal alleles. Im- printed genes (14–17). printing has been tied to the evolution of the placenta in mammals Advances in DNA sequencing technology have been leveraged and defects of imprinting have been associated with human dis- for high-throughput identification of imprinted genes. The “BS- eases. Although recent advances in genome sequencing have revo- seq” technology couples bisulfite treatment with high-throughput lutionized the study of DNA methylation, existing methylome data short-read sequencing, and has enabled genome-wide profiling of remain largely untapped in the study of imprinting. We present a DNA methylation in mammalian genomes at single-CpG (cyto- statistical model to describe allele-specific methylation (ASM) in sine guanine dinucleotide) resolution (18). Li et al. (19) produced data from high-throughput short-read bisulfite sequencing. Simula- a methylome from peripheral blood of a single individual and tion results indicate technical specifications of existing methylome recognized the potential of using such data to profile ASM. -
Adenosine Monophosphate Deaminase 3 Activation Shortens Erythrocyte Half-Life and Provides Malaria Resistance in Mice
From www.bloodjournal.org by guest on January 20, 2017. For personal use only. Regular Article RED CELLS, IRON, AND ERYTHROPOIESIS Adenosine monophosphate deaminase 3 activation shortens erythrocyte half-life and provides malaria resistance in mice Elinor Hortle,1 Brunda Nijagal,2 Denis C. Bauer,3 Lora M. Jensen,1 Seong Beom Ahn,4 Ian A. Cockburn,1 Shelley Lampkin,1 Dedreia Tull,2 Malcolm J. McConville,5 Brendan J. McMorran,1 Simon J. Foote,1 and Gaetan Burgio1 1Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia; 2Metabolomics Australia, Bio21 Institute, University of Melbourne, Parkville, VIC, Australia; 3Commonwealth Scientific and Industrial Research Organization, Sydney, NSW, Australia; 4Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia; and 5Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, VIC, Australia Key Points The factors that determine red blood cell (RBC) lifespan and the rate of RBC aging have not been fully elucidated. In several genetic conditions, including sickle cell disease, • AMPD3 activation reduces thalassemia, and G6PD deficiency, erythrocyte lifespan is significantly shortened. Many red blood cell half-life, which of these diseases are also associated with protection from severe malaria, suggesting is associated with increased a role for accelerated RBC senescence and clearance in malaria resistance. Here, we re- oxidative stress and port a novel, N-ethyl-N-nitrosourea–induced mutation that causes a gain of function in phosphatidylserine exposure. adenosine 59-monophosphate deaminase (AMPD3). Mice carrying the mutation exhibit • AMPD3 activation causes rapid RBC turnover, with increased erythropoiesis, dramatically shortened RBC lifespan, and signs of increased RBC senescence/eryptosis, suggesting a key role for AMPD3 in malaria resistance through determining RBC half-life. -
Supporting Information
Supporting Information Miller et al. 10.1073/pnas.0914257107 SI Materials and Methods files with 20 to 40 samples and 5,629 to 9,731 genes each and 20 Data Set Acquisition and Filtering. All data sets were downloaded mouse expression files with 18 and 44 samples and 5,176 to 6,157 from the GEO database, and consisted of experiments run on genes each. All preprocessed data files (as well as the resulting either mouse or human brain tissue (Fig. 1A). We filtered out all network data and some associated code and support files) are but a core collection of data sets that were similar enough for available at the WGCNA group Web site (www.genetics.ucla.edu/ useful bioinformatic comparison. First, we removed all data sets labs/horvath/CoexpressionNetwork/MouseHumanBrain). that were not run on an Affymetrix platform, leaving three From these preprocessed expression files we created a human platforms in human (HG-U95A, HG-U133A, HG-U133 Plus 2) and a mouse consensus network (method modified from ref. 4). and two in mouse (MG-U74A, MG-U430A). Second, we ex- For each consensus network we first created correlation matrices cluded all samples in each data set that were not taken from from each data set (obtained by calculating the Pearson correla- brain tissue (for example, in one expression atlas study, more tions between all variable probe sets across all subjects in each than 80% of the samples were excluded). Third, to make the data set), and then weighted them based on the number of sam- correlations between genes more comparable across studies, we ples used in that data set. -
Masseter Muscle Gene Expression in Relation to Various Craniofacial Deformities: a Genotype-Phenotype Study
Masseter muscle gene expression in relation to various craniofacial deformities: A genotype-phenotype study Hadwah AbdelMatloub Moawad B.D.S Dental College/ King Saud University (Saudi Arabia) M.Sc in Orthodontics Eastman Dental Institute/ University of London (UK) A thesis submitted for the degree of Doctor of Philosophy Division of Craniofacial Developmental Sciences, Orthodontic Unit UCL Eastman Dental Institute, UK 2009 Dedication To my beloved parents My sisters: Ruba Anadel Ranad My brother: Mohamed You are the greatest treasure of my life and without your love, support and prayers I would have never produced this work ABSTRACT Craniofacial form is defined by a number of factors. A major contributor is the jaw musculature especially of the masseter muscle, as differences in transcription and translation of various genes have been documented from this tissue. Up to this point however, no reliable biological predictors of form have been identified. The aims of this study were therefore, to describe the transcriptome of the masseter muscle using microarray technology and to establish and correlate the expression levels of potential candidate and known “informative” genes in masseter muscle with selected clinical, radiographic and dental features of subjects with a variety of craniofacial morphologies. A total of 29 patients (18 deformity and 11 control) were selected from the orthodontic/orthognathic clinics at the Eastman Dental and Whipps Cross Hospitals, London, and Riyadh Military Hospital, Saudi Arabia. Microarray results indicated five “novel” genes not previously reported in relation to the masseter muscles of subjects with variable craniofacial morphologies. Two genes (KIAA1671 and DGCR6) were down-regulated in long face patients, one (SERGEF) was down-regulated in Class III patients and one (LOC730245) was up-regulated in Class II long faces and in all Class III subjects, compared to controls. -
Genomic Landscape of Human Allele-Specific DNA Methylation
Genomic landscape of human allele-specific DNA methylation Fang Fanga, Emily Hodgesb, Antoine Molarob, Matthew Deana, Gregory J. Hannonb, and Andrew D. Smitha,1 aMolecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, California; and bHoward Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724 Edited by Wing Hung Wong, Stanford University, Stanford, CA, and approved March 8, 2012 (received for review January 24, 2012) DNA methylation mediates imprinted gene expression by passing stages preceding the context in which they become active. Such an epigenomic state across generations and differentially marking methods have been successfully applied to identify unique im- specific regulatory regions on maternal and paternal alleles. Im- printed genes (14–17). printing has been tied to the evolution of the placenta in mammals Advances in DNA sequencing technology have been leveraged and defects of imprinting have been associated with human dis- for high-throughput identification of imprinted genes. The “BS- eases. Although recent advances in genome sequencing have revo- seq” technology couples bisulfite treatment with high-throughput lutionized the study of DNA methylation, existing methylome data short-read sequencing, and has enabled genome-wide profiling of remain largely untapped in the study of imprinting. We present a DNA methylation in mammalian genomes at single-CpG (cyto- statistical model to describe allele-specific methylation (ASM) in sine guanine dinucleotide) resolution (18). Li et al. (19) produced data from high-throughput short-read bisulfite sequencing. Simula- a methylome from peripheral blood of a single individual and tion results indicate technical specifications of existing methylome recognized the potential of using such data to profile ASM. -
An Investigation of the Antigastric Cancer Effect in Tumor Microenvironment of Radix Rhei Et Rhizome: a Network Pharmacology Study
Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2021, Article ID 9913952, 9 pages https://doi.org/10.1155/2021/9913952 Research Article An Investigation of the Antigastric Cancer Effect in Tumor Microenvironment of Radix Rhei Et Rhizome: A Network Pharmacology Study Xinmiao Wang ,1 Guanghui Zhu ,1,2 Haoyu Yang ,1,2 Ruike Gao ,1 Zhe Wu ,1 Ying Zhang,1 Xiaoyu Zhu,1 Xiaoxiao Zhang,1 and Jie Li 1 1Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China 2Beijing University of Traditional Chinese Medicine, Beijing 100029, China Correspondence should be addressed to Jie Li; [email protected] Received 27 March 2021; Revised 20 May 2021; Accepted 11 June 2021; Published 24 June 2021 Academic Editor: Yibin Feng Copyright © 2021 Xinmiao Wang et al. +is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. Tumor microenvironment (TME) takes a vital effect on the occurrence and development of cancer. Radix Rhei Et Rhizome (RRER, Da-Huang in pinyin), a classical Chinese herb, has been widely used in gastric cancer (GC) for many years in China. However, inadequate systematic studies have focused on the anti-GC effect of RRER in TME. +is study intended to uncover the mechanism of it by network pharmacology. Methods. We collected compounds and targets of RRER from traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) and SwissTargetPrediction. GC targets were obtained from GeneCards. Protein- protein interaction (PPI) network and RRER-GC-target network were built by STRING and Cytoscape 3.2.1. -
Characterization of Global Loss of Imprinting in Fetal Overgrowth Syndrome Induced by Assisted Reproduction
Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction Zhiyuan Chena, Darren E. Hagena, Christine G. Elsika, Tieming Jib, Collin James Morrisc, Laura Emily Moond, and Rocío Melissa Riveraa,1 aDivision of Animal Sciences, bDepartment of Statistics, cDepartment of Biological Sciences, and dDepartment of Bioengineering, University of Missouri, Columbia, MO 65211 Edited by George E. Seidel, Colorado State University, Fort Collins, CO, and approved February 24, 2015 (received for review November 20, 2014) Embryos generated with the use of assisted reproductive technol- studies in animals (5–8) and retrospective studies in humans (9) ogies (ART) can develop overgrowth syndromes. In ruminants, the have shown that ART can induce improper regulation of geno- condition is referred to as large offspring syndrome (LOS) and mic imprinting. ART is commonly used in clinics to treat sub- exhibits variable phenotypic abnormalities including overgrowth, fertility and infertility, and each year as high as 5.9% of infants enlarged tongue, and abdominal wall defects. These character- born in developed countries are conceived by the use of these istics recapitulate those observed in the human loss-of-imprinting technologies (10, 11). In agriculture, ART is also widely used to (LOI) overgrowth syndrome Beckwith–Wiedemann (BWS). We increase the number of offspring produced from genetically su- have recently shown LOI at the KCNQ1 locus in LOS, the most perior individuals in a shortened period (12). Multiple reports common epimutation in BWS. Although the first case of ART- have indicated that ART-conceived offspring are more likely to induced LOS was reported in 1995, studies have not yet deter- develop imprinting disorders such as Beckwith–Wiedemann mined the extent of LOI in this condition.