Project description:Microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent and related functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics via nano-2D-LC-MS/MS to simultaneously monitor microbial and human proteins in fecal samples from a healthy preterm infant during early development. ). All MS/MS spectra were searched against a predicted protein database containing 25 microbial species along with the Human RefSeq2011 genome using the SEQUEST algorithm (Eng et al, 1994), and filtered with DTASelect version 1.9 (Tabb et al, 2002) at the peptide level with standard filters [SEQUEST Xcorrs of at least 1.8 (+1), 2.5 (+2) 3.5 (+3)] organizing identified peptides to their corresponding protein sequences. This study provides the first elucidation of coordinated human and microbial proteins in the infant gut during early development.
Project description:Extensive molecular and prognostic characterization of wild-type MLL infant ALL. Background: Approximately 20% of all infant ALL cases carry wild-type (or germline) MLL genes. To date, wild-type MLL infant ALL patients are generally regarded as young pediatric precursor B-ALL patients, but extensive characterization of this specific patient group largely remains unacknowledged. Methods: We here studied a relatively large cohort of 78 wild-type MLL infant ALL samples, using clinical parameters, array-comparative genomic hybridization analysis, gene expression profiling, multiplex ligation-dependent probe amplification, and conventional sequencing. Findings: Wild-type MLL infant ALL patients are generally characterized by a lower incidence of favourable prognostic factors than pediatric (non-infant) B-ALL patients, and patients at high risk of therapy failure typically display an immature pro-B immunophenotype or respond poorly to prednisone. Using gene expression profiling, we found MEIS1 expression to additionally be highly predictive for clinical outcome in wild-type MLL infant ALL with a favourable prognosis in the wild-type MLL infants with low MEIS1 expression (DFS 88%% versus 50%, p=0•01). Overall the incidence of DNA copy number variations and genetic abnormalities in genes involved in B-cell differentiation is lower in wild-type MLL infant ALL patients as compared with pediatric precursor B-ALL patients. Interpretation: Wild-type MLL infant ALL represents a highly heterogeneous patient group, which cannot be unified by one or a few known recurrent genomic aberrations. High-level MEIS1 expression and an immature pro-B immunophenotype in high-risk wild-type MLL infant ALL patients shows parallel with the unfavourable prognosis of MLL-rearranged infant ALL patients. In contrast, wild-type MLL infant ALL patients expressing lower levels of MEIS1 and displaying more differentiated (pre-B or common) phenotypes may well be more related to pediatric precursor B-ALL patients older than 1 year of age. We advocate that a treatment strategy in wild-type MLL infant ALL based on MEIS1 expression could be beneficial for improving survival. Gene expression profiling of wild-type MLL infant ALL. Additional wild-type MLL infant ALL patient samples (n=17) to the earlier samples published under GSE19475 (GSM485309 to GSM485322).