PubMed Health⌕ Search

PubMed · 15001475

CisML: an XML-based format for sequence motif detection software.

Abstract

SUMMARY: CisML is an XML-based format for sequence motif detection software. This proposed standard is applicable to many types of sequence motif detection programs. It is intended to facilitate the integration of data and the comparison of results from different software packages, and to simplify the development of downstream tools. XSL stylesheets are provided for easy generation of text, html and graphical reports from CisML-formatted data. AVAILABILITY: http://zlab.bu.edu/CisML/ SUPPLEMENTARY INFORMATION: Example CisML-formatted data and XSL stylesheets for report generation are available along with the sample output.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Peter M Haverty, Zhiping Weng. 2004-03-04. CisML: an XML-based format for sequence motif detection software.. https://doi.org/10.1093/bioinformatics%2Fbth162

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

GAMMA: gap-aware motif mining under incomplete labeling with applications to MHC motifs.

MOTIVATION: Sequence motif identification is crucial for understanding molecular recognition, particularly in immune responses involving peptide binding to major histocompatibility complex (MHC) Class I molecules for antigen presentation to T cells. Traditionally, MHC Class I binding motifs are assumed to be contiguous and span nine amino acids. However, structural evidence suggests that binding may involve nonadjacent residues, challenging the assumptions of existing methods. RESULTS: In this study, we propose Gap-Aware Motif Mining Algorithm (GAMMA), a probabilistic framework designed to identify noncontiguous motifs under conditions of incomplete labeling. GAMMA employs Bayesian inference with Markov chain Monte Carlo sampling to jointly estimate motif parameters, binding locations, and the relative spacing between binding positions. Through extensive simulations and real-world applications to MHC Class I peptide datasets, GAMMA outperforms existing motif discovery tools such as GLAM2 in accurately localizing binding residues and identifying the underlying motifs. Notably, our results suggest that the true number of binding residues may be eight, fewer than the commonly assumed nine. In addition, for longer peptides, the model captures increased flexibility in the central region, consistent with structural observations that peptides may bulge in the middle. AVAILABILITY AND IMPLEMENTATION: The raw data and the source codes are available on GitHub (https://github.com/RanLIUaca/GAMMAmotif).

Amino Acid Motifs↗

Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia.

B cells are selected for an intermediate level of B-cell antigen receptor (BCR) signalling strength: attenuation below minimum (for example, non-functional BCR) or hyperactivation above maximum (for example, self-reactive BCR) thresholds of signalling strength causes negative selection. In ∼25% of cases, acute lymphoblastic leukaemia (ALL) cells carry the oncogenic BCR-ABL1 tyrosine kinase (Philadelphia chromosome positive), which mimics constitutively active pre-BCR signalling. Current therapeutic approaches are largely focused on the development of more potent tyrosine kinase inhibitors to suppress oncogenic signalling below a minimum threshold for survival. We tested the hypothesis that targeted hyperactivation--above a maximum threshold--will engage a deletional checkpoint for removal of self-reactive B cells and selectively kill ALL cells. Here we find, by testing various components of proximal pre-BCR signalling in mouse BCR-ABL1 cells, that an incremental increase of Syk tyrosine kinase activity was required and sufficient to induce cell death. Hyperactive Syk was functionally equivalent to acute activation of a self-reactive BCR on ALL cells. Despite oncogenic transformation, this basic mechanism of negative selection was still functional in ALL cells. Unlike normal pre-B cells, patient-derived ALL cells express the inhibitory receptors PECAM1, CD300A and LAIR1 at high levels. Genetic studies revealed that Pecam1, Cd300a and Lair1 are critical to calibrate oncogenic signalling strength through recruitment of the inhibitory phosphatases Ptpn6 (ref. 7) and Inpp5d (ref. 8). Using a novel small-molecule inhibitor of INPP5D (also known as SHIP1), we demonstrated that pharmacological hyperactivation of SYK and engagement of negative B-cell selection represents a promising new strategy to overcome drug resistance in human ALL.

Amino Acid Motifs↗

Reconstitution of Runx2/Cbfa1-null cells identifies a requirement for BMP2 signaling through a Runx2 functional domain during osteoblast differentiation.

The Runx2/Cbfa1 transcription factor is a scaffolding protein that promotes osteoblast differentiation; however, the specific Runx2-functional domains required for induction of the osteogenic lineage remain to be identified. We approached this question using a TERT-immortalized cell line derived from calvaria of Runx2-null mice by reconstituting the osteogenic activity with wild-type and deletion mutants of Runx2. The presence or absence of osteogenic media (beta-glycerol phosphate and ascorbic acid) and/or with BMP2 did not stimulate osteoblastic gene expression in the Runx2-null cells. However, cells infected with wild-type Runx2 adenovirus showed a robust temporal increase in the expression of osteoblast marker genes and were competent to respond to BMP2. Early markers (i.e., collagen type-1, alkaline phosphatase) were induced (four- to eightfold) at Days 4 and 8 of culture. Genes representing mature osteoblasts (e.g., Runx2, osteopontin, bone sialoprotein, osteocalcin) were temporally expressed and induced from 18- to 36-fold at Days 8 and 12. Interestingly, TGFbeta and Vitamin D-mediated transcription of osteoblast genes (except for osteopontin) required the presence of Runx2. Runx2 lacking the C-terminal 96 amino acids (Runx2 Delta432) showed a pattern of gene expression similar to wild-type protein, demonstrating the Groucho interaction and part of the activation domain are dispensable for Runx2 osteogenic activity. Upon further deletion of the Runx2 C-terminus containing the nuclear matrix targeting signal and Smad-interacting domain (Delta391), we find none of the osteoblast markers are expressed. Therefore, the Runx2 391-432 domain is essential for execution of the BMP2 osteogenic signal.

Amino Acid Motifs↗