RESUMO
BACKGROUND: Bacterial resistance to antibiotics is a growing health problem that is projected to cause more deaths than cancer by 2050. Consequently, novel antibiotics are urgently needed. Since more than half of the available antibiotics target the structurally conserved bacterial ribosomes, factors involved in protein synthesis are thus prime targets for the development of novel antibiotics. However, experimental identification of these potential antibiotic target proteins can be labor-intensive and challenging, as these proteins are likely to be poorly characterized and specific to few bacteria. Here, we use a bioinformatics approach to identify novel components of protein synthesis. RESULTS: In order to identify these novel proteins, we established a Large-Scale Transcriptomic Analysis Pipeline in Crowd (LSTrAP-Crowd), where 285 individuals processed 26 terabytes of RNA-sequencing data of the 17 most notorious bacterial pathogens. In total, the crowd processed 26,269 RNA-seq experiments and used the data to construct gene co-expression networks, which were used to identify more than a hundred uncharacterized genes that were transcriptionally associated with protein synthesis. We provide the identity of these genes together with the processed gene expression data. CONCLUSIONS: We identified genes related to protein synthesis in common bacterial pathogens and thus provide a resource of potential antibiotic development targets for experimental validation. The data can be used to explore additional vulnerabilities of bacteria, while our approach demonstrates how the processing of gene expression data can be easily crowd-sourced.
Assuntos
Bactérias/genética , Biologia Computacional/métodos , Crowdsourcing , Perfilação da Expressão Gênica/métodos , Expressão Gênica , Ribossomos/química , Análise de Sequência de RNA/métodos , Redes Reguladoras de GenesRESUMO
As genomes become more and more available, gene function prediction presents itself as one of the major hurdles in our quest to extract meaningful information on the biological processes genes participate in. In order to facilitate gene function prediction, we show how our user-friendly pipeline, the Large-Scale Transcriptomic Analysis Pipeline in Cloud (LSTrAP-Cloud), can be useful in helping biologists make a shortlist of genes involved in a biological process that they might be interested in, by using a single gene of interest as bait. The LSTrAP-Cloud is based on Google Colaboratory, and provides user-friendly tools that process quality-control RNA sequencing data streamed from the European Nucleotide Archive. The LSTRAP-Cloud outputs a gene coexpression network that can be used to identify functionally related genes for any organism with a sequenced genome and publicly available RNA sequencing data. Here, we used the biosynthesis pathway of Nicotiana tabacum as a case study to demonstrate how enzymes, transporters, and transcription factors involved in the synthesis, transport, and regulation of nicotine can be identified using our pipeline.
Assuntos
Computação em Nuvem/estatística & dados numéricos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Análise de Sequência de RNA/métodos , Software , Interface Usuário-Computador , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , HumanosRESUMO
Placenta accreta is now the chief cause of postpartum hemorrhage resulting in maternal and neonatal morbidity. Prenatal diagnosis decreases blood loss at delivery and intra and post-partum complications. Ultrasound is critical for diagnosis and MRI is a complementary tool when the diagnosis is uncertain. Peripartum hysterectomy has been the standard of therapy but conservative management is increasingly being used. The etiology of accreta is due to a deficiency of maternal decidua resulting in placental invasion into the uterine myometrium. The molecular basis for the development of invasive placentation is yet to be elucidated but may involve abnormal paracrine/autocrine signaling between the deficient maternal decidua and the trophoblastic tissue. The interaction of hormones such as Relaxin which is abundant in maternal decidua and insulin-like 4, an insulin-like peptide found in placental trophoblastic tissue may play role in the formation of placenta accreta.
Assuntos
Placenta Acreta/diagnóstico por imagem , Feminino , Humanos , Programas de Rastreamento , Placenta Acreta/etiologia , Placenta Acreta/cirurgia , GravidezRESUMO
PURPOSE OF REVIEW: With the increased use of ultrasonography in the first trimester, up to 1% of all pregnancies are diagnosed with an adnexal mass. Yet, the management of asymptomatic adnexal masses in pregnancy continues to be controversial as management guidelines are mainly based on case-control or observational studies. The purpose of this article was to review the recent literature and provide clinical guidance on patient management. RECENT FINDINGS: This review will highlight the increasing sensitivity of ultrasound imaging in diagnosing the rare malignant lesion, allowing for antenatal expectant management of benign asymptomatic adnexal masses until delivery or postpartum. The recent literature also highlights the well tolerated use of laparoscopy for the antenatal removal of suspicious or symptomatic masses and that expectant management of asymptomatic masses does not increase the risk of adverse pregnancy outcomes. SUMMARY: Most adnexal masses are benign and ultrasound characteristics can help guide the assessment of asymptomatic ovarian masses. When surgical management is chosen, laparoscopy can be safely performed in pregnancy. Ovarian torsion is a complication for persistent masses in pregnancy.
Assuntos
Doenças dos Anexos/diagnóstico por imagem , Antígeno Ca-125/metabolismo , Cistos Ovarianos/diagnóstico por imagem , Neoplasias Ovarianas/diagnóstico por imagem , Complicações Neoplásicas na Gravidez/diagnóstico por imagem , Doenças dos Anexos/patologia , Doenças dos Anexos/cirurgia , Adulto , Biomarcadores Tumorais/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Achados Incidentais , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Guias de Prática Clínica como Assunto , Gravidez , Complicações Neoplásicas na Gravidez/patologia , Complicações Neoplásicas na Gravidez/cirurgia , Resultado da Gravidez , Trimestres da Gravidez , Ruptura , Sensibilidade e Especificidade , Resultado do Tratamento , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. METHODS: This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. RESULTS: A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. CONCLUSION: A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.