FOAM (functional ontology assignments for metagenomes):a hidden markov model (HMM) database with environmental focus

A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. ‘profiles’) were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/

A Marfan syndrome human induced pluripotent stem cell line with a heterozygous FBN1 c.4082G>A mutation, ISMMSi002-B, for disease modeling

Fibroblasts of a 28-year-old female with Marfan syndrome (MFS) due to a heterozygous FBN1 c.4082G>A mutation were reprogrammed using the Sendai virus delivery method. The established human induced pluripotent stem cell (hiPSC) line named ISMMSi002-B expresses pluripotency markers, has a normal karyotype, carries the specific FBN1 mutation and is able to differentiate into three germ layers in vitro. ISMMSi002-B has utility in studying MFS pathogenesis, including skeletal abnormalities, cardiomyopathy, and vascular smooth muscle cell dysfunction associated with aortic aneurysm. Furthermore, it can serve as a platform for drug discovery

FOAM (Functional Ontology Assignments for Metagenomes): a Hidden Markov Model (HMM) database with environmental focus

To the best of our knowledge, one or more authors of this paper were federal employees when contributing to this work. This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Oxford University Press. The published article can be found at: http://nar.oxfordjournals.org/.A new functional gene database, FOAM (Functional\ud Ontology Assignments for Metagenomes), was developed\ud to screen environmental metagenomic sequence\ud datasets. FOAM provides a new functional\ud ontology dedicated to classify gene functions relevant\ud to environmental microorganisms based on Hidden\ud Markov Models (HMMs). Sets of aligned protein\ud sequences (i.e. ‘profiles’) were tailored to a large\ud group of target KEGG Orthologs (KOs) from which\ud HMMs were trained. The alignments were checked\ud and curated to make them specific to the targeted\ud KO. Within this process, sequence profiles were enriched\ud with the most abundant sequences available\ud to maximize the yield of accurate classifier models.\ud An associated functional ontology was built to describe\ud the functional groups and hierarchy. FOAM\ud allows the user to select the target search space\ud before HMM-based comparison steps and to easily\ud organize the results into different functional categories\ud and subcategories. FOAM is publicly available\ud at http://portal.nersc.gov/project/m1317/FOAM/

FOAM (Functional Ontology Assignments for Metagenomes): a Hidden Markov Model (HMM) database with environmental focus.

A new functional gene database, FOAM (Functional Ontology Assignments for Metagenomes), was developed to screen environmental metagenomic sequence datasets. FOAM provides a new functional ontology dedicated to classify gene functions relevant to environmental microorganisms based on Hidden Markov Models (HMMs). Sets of aligned protein sequences (i.e. 'profiles') were tailored to a large group of target KEGG Orthologs (KOs) from which HMMs were trained. The alignments were checked and curated to make them specific to the targeted KO. Within this process, sequence profiles were enriched with the most abundant sequences available to maximize the yield of accurate classifier models. An associated functional ontology was built to describe the functional groups and hierarchy. FOAM allows the user to select the target search space before HMM-based comparison steps and to easily organize the results into different functional categories and subcategories. FOAM is publicly available at http://portal.nersc.gov/project/m1317/FOAM/

Dysregulation of astrocyte extracellular signaling in Costello syndrome

Astrocytes produce an assortment of signals that promote neuronal maturation according to a precise developmental timeline. Is this orchestrated timing and signaling altered in human neurodevelopmental disorders? To address this question, the astroglial lineage was investigated in two model systems of a developmental disorder with intellectual disability caused by mutant Harvey rat sarcoma viral oncogene homolog (HRAS) termed Costello syndrome: mutant HRAS human induced pluripotent stem cells (iPSCs) and transgenic mice. Human iPSCs derived from patients with Costello syndrome differentiated to astroglia more rapidly in vitro than those derived from wild-type cell lines with normal HRAS, exhibited hyperplasia, and also generated an abundance of extracellular matrix remodeling factors and proteoglycans. Acute treatment with a farnesyl transferase inhibitor and knockdown of the transcription factor SNAI2 reduced expression of several proteoglycans in Costello syndrome iPSC-derived astrocytes. Similarly, mice in which mutant HRAS was expressed selectively in astrocytes exhibited experience-independent increased accumulation of perineuronal net proteoglycans in cortex, as well as increased parvalbumin expression in interneurons, when compared to wild-type mice. Our data indicate that astrocytes expressing mutant HRAS dysregulate cortical maturation during development as shown by abnormal extracellular matrix remodeling and implicate excessive astrocyte-to-neuron signaling as a possible drug target for treating mental impairment and enhancing neuroplasticity