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Geistlinger, L.

Publications and source records attributed to Geistlinger, L..

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HMP16SData: Efficient Access to the Human Microbiome Project through Bioconductor

Phase 1 of the NIH Human Microbiome Project (HMP) investigated 18 body subsites of 239 healthy American adults, to produce the first comprehensive reference for the composition and variation of the \"healthy\" human microbiome. Publicly-available data sets from amplicon sequencing of two 16S rRNA variable regions, with extensive controlled-access participant data, provide a reference for ongoing microbiome studies. However, utilization of these data sets can be hindered by the complex bioinformatic steps required to access, import, decrypt, and merge the various components in formats suitable for ecological and statistical analysis. The HMP16SData package provides count data for both 16S variable regions, integrated with phylogeny, taxonomy, public participant data, and controlled participant data for authorized researchers, using standard integrative Bioconductor data objects. By removing bioinformatic hurdles of data access and management, HMP16SData enables epidemiologists with only basic R skills to quickly analyze HMP data.

bioinformatics

A comprehensive manually-curated Compendium of Bovine Transcription Factors

Transcription factors (TFs) are pivotal regulatory proteins that control gene expression in a context-dependent and tissue-specific manner. In contrast to human, where comprehensive curated TF collections exist, bovine TFs are only rudimentary recorded and characterized. In this article, we present a manually-curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we analyzed for domain family distribution, evolutionary conservation, and tissue-specific expression. In addition, we provide a list of putative transcription cofactors derived from known interactions with the identified TFs. Since there is a general lack of knowledge concerning the regulation of gene expression in cattle, the curated list of TF should provide a basis for an improved comprehension of regulatory mechanisms that are specific to the species.

genomics

Consensus on Molecular Subtypes of Ovarian Cancer

INTRODUCTIONVarious computational methods for gene expression-based subtyping of high-grade serous (HGS) ovarian cancer have been proposed. This resulted in the identification of molecular subtypes that are based on different datasets and were differentially validated, making it difficult to achieve consensus on which definitions to use in follow-up studies. We assess three major subtype classifiers for their robustness and association to outcome by a meta-analysis of publicly available expression data, and provide a classifier that represents their consensus.\n\nMETHODSWe use a compendium of 15 microarray datasets consisting of 1,774 HGS ovarian tumors to assess 1) concordance between published subtyping algorithms, 2) robustness of those algorithms to re-clustering across datasets, and 3) association of subtypes with overall survival. A consensus classifier is trained on concordantly classified samples, and validated by leave-one-dataset-out validation.\n\nRESULTSEach subtyping classifier identified subsets significantly differing in overall survival, but were not robust to re-fitting in independent datasets and grouped only approximately one third of patients concordantly into four subtypes. We propose a consensus classifier to identify the minority of unambiguously classifiable tumors across multiple gene expression platforms, using a 100-gene signature. The resulting consensus subtypes correlate with patient age, survival, tumor purity, and lymphocyte infiltration.\n\nCONCLUSIONSOur analysis demonstrates that most HGS ovarian cancers are not able to be subtyped. A minority of tumors can be classified and our proposed consensus classifier consolidates and improves on the robustness of three previously proposed subtype classifiers. It provides reliable stratification of patients with HGS ovarian tumors of clearly defined subtype, and will assist in studying the role of polyclonality in the majority of tumors that are not robustly classifiable.

cancer biology