LIVIVO - Search results -

Search results

Result 1 - 9 of total 9

Search options

Article ; Online: The distance-profile representation and its application to detection of distantly related protein families

Yona Golan / Ku Chin-Jen

BMC Bioinformatics, Vol 6, Iss 1, p

2005 Volume 282

Abstract: Abstract Background Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many ... ...

Abstract	Abstract Background Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many existing approaches address this problem by measuring the similarity between proteins through sequence or structural alignment. However, these methods do not exploit collective aspects of the protein space and the computed scores are often noisy and frequently fail to recognize distantly related protein families. Results We describe an algorithm that improves over the state of the art in homology detection by utilizing global information on the proximity of entities in the protein space. Our method relies on a vectorial representation of proteins and protein families and uses structure-specific association measures between proteins and template structures to form a high-dimensional feature vector for each query protein. These vectors are then processed and transformed to sparse feature vectors that are treated as statistical fingerprints of the query proteins. The new representation induces a new metric between proteins measured by the statistical difference between their corresponding probability distributions. Conclusion Using several performance measures we show that the new tool considerably improves the performance in recognizing distant homologies compared to existing approaches such as PSIBLAST and FUGUE.
Keywords	Computer applications to medicine. Medical informatics ; R858-859.7 ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2005-11-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: The Cell Type-Specific 5hmC Landscape and Dynamics of Healthy Human Hematopoiesis and TET2-Mutant Preleukemia.

Nakauchi, Yusuke / Azizi, Armon / Thomas, Daniel / Corces, M Ryan / Reinisch, Andreas / Sharma, Rajiv / Cruz Hernandez, David / Köhnke, Thomas / Karigane, Daiki / Fan, Amy / Martinez-Krams, Daniel / Stafford, Melissa / Kaur, Satinder / Dutta, Ritika / Phan, Paul / Ediriwickrema, Asiri / McCarthy, Erin / Ning, Yuhong / Phillips, Tierney /

Ellison, Christopher K / Guler, Gulfem D / Bergamaschi, Anna / Ku, Chin-Jen / Levy, Samuel / Majeti, Ravindra

Blood cancer discovery

2022 Volume 3, Issue 4, Page(s) 346–367

Abstract: The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that is mediated by ten-eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape of normal ... ...

Abstract	The conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) is a key step in DNA demethylation that is mediated by ten-eleven translocation (TET) enzymes, which require ascorbate/vitamin C. Here, we report the 5hmC landscape of normal hematopoiesis and identify cell type-specific 5hmC profiles associated with active transcription and chromatin accessibility of key hematopoietic regulators. We utilized CRISPR/Cas9 to model TET2 loss-of-function mutations in primary human hematopoietic stem and progenitor cells (HSPC). Disrupted cells exhibited increased colonies in serial replating, defective erythroid/megakaryocytic differentiation, and in vivo competitive advantage and myeloid skewing coupled with reduction of 5hmC at erythroid-associated gene loci. Azacitidine and ascorbate restored 5hmC abundance and slowed or reverted the expansion of TET2-mutant clones in vivo. These results demonstrate the key role of 5hmC in normal hematopoiesis and TET2-mutant phenotypes and raise the possibility of utilizing these agents to further our understanding of preleukemia and clonal hematopoiesis. Significance: We show that 5-hydroxymethylation profiles are cell type-specific and associated with transcriptional abundance and chromatin accessibility across human hematopoiesis. TET2 loss caused aberrant growth and differentiation phenotypes and disrupted 5hmC and transcriptional landscapes. Treatment of TET2 KO HSPCs with ascorbate or azacitidine reverted 5hmC profiles and restored aberrant phenotypes. This article is highlighted in the In This Issue feature, p. 265.
MeSH term(s)	Azacitidine/pharmacology ; Chromatin/genetics ; DNA-Binding Proteins/genetics ; Dioxygenases/genetics ; Hematopoiesis/genetics ; Humans ; Myelodysplastic Syndromes ; Preleukemia ; Proto-Oncogene Proteins/genetics
Chemical Substances	Chromatin ; DNA-Binding Proteins ; Proto-Oncogene Proteins ; Dioxygenases (EC 1.13.11.-) ; TET2 protein, human (EC 1.13.11.-) ; Azacitidine (M801H13NRU)
Language	English
Publishing date	2022-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	3028898-8
ISSN	2643-3249 ; 2643-3230
ISSN (online)	2643-3249
ISSN	2643-3230
DOI	10.1158/2643-3230.BCD-21-0143
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: The distance-profile representation and its application to detection of distantly related protein families.

Ku, Chin-Jen / Yona, Golan

BMC bioinformatics

2005 Volume 6, Page(s) 282

Abstract: Background: Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many existing ... ...

Abstract	Background: Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many existing approaches address this problem by measuring the similarity between proteins through sequence or structural alignment. However, these methods do not exploit collective aspects of the protein space and the computed scores are often noisy and frequently fail to recognize distantly related protein families. Results: We describe an algorithm that improves over the state of the art in homology detection by utilizing global information on the proximity of entities in the protein space. Our method relies on a vectorial representation of proteins and protein families and uses structure-specific association measures between proteins and template structures to form a high-dimensional feature vector for each query protein. These vectors are then processed and transformed to sparse feature vectors that are treated as statistical fingerprints of the query proteins. The new representation induces a new metric between proteins measured by the statistical difference between their corresponding probability distributions. Conclusion: Using several performance measures we show that the new tool considerably improves the performance in recognizing distant homologies compared to existing approaches such as PSIBLAST and FUGUE.
MeSH term(s)	Algorithms ; Animals ; Computational Biology/methods ; Databases, Protein ; Genetic Vectors ; Humans ; Models, Statistical ; Multigene Family ; Probability ; Proteins/chemistry ; Sequence Alignment/methods ; Sequence Analysis, Protein ; Software
Chemical Substances	Proteins
Language	English
Publishing date	2005-11-29
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2041484-5
ISSN	1471-2105 ; 1471-2105
ISSN (online)	1471-2105
ISSN	1471-2105
DOI	10.1186/1471-2105-6-282
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Full text

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA.

Guler, Gulfem D / Ning, Yuhong / Ku, Chin-Jen / Phillips, Tierney / McCarthy, Erin / Ellison, Christopher K / Bergamaschi, Anna / Collin, Francois / Lloyd, Paul / Scott, Aaron / Antoine, Michael / Wang, Wendy / Chau, Kim / Ashworth, Alan / Quake, Stephen R / Levy, Samuel

Nature communications

2020 Volume 11, Issue 1, Page(s) 5270

Abstract: Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a ... ...

Abstract	Pancreatic cancer is often detected late, when curative therapies are no longer possible. Here, we present non-invasive detection of pancreatic ductal adenocarcinoma (PDAC) by 5-hydroxymethylcytosine (5hmC) changes in circulating cell free DNA from a PDAC cohort (n = 64) in comparison with a non-cancer cohort (n = 243). Differential hydroxymethylation is found in thousands of genes, most significantly in genes related to pancreas development or function (GATA4, GATA6, PROX1, ONECUT1, MEIS2), and cancer pathogenesis (YAP1, TEAD1, PROX1, IGF1). cfDNA hydroxymethylome in PDAC cohort is differentially enriched for genes that are commonly de-regulated in PDAC tumors upon activation of KRAS and inactivation of TP53. Regularized regression models built using 5hmC densities in genes perform with AUC of 0.92 (discovery dataset, n = 79) and 0.92-0.94 (two independent test sets, n = 228). Furthermore, tissue-derived 5hmC features can be used to classify PDAC cfDNA (AUC = 0.88). These findings suggest that 5hmC changes enable classification of PDAC even during early stage disease.
MeSH term(s)	5-Methylcytosine/analogs & derivatives ; 5-Methylcytosine/metabolism ; Adult ; Biomarkers, Tumor/blood ; Biomarkers, Tumor/metabolism ; Cell-Free Nucleic Acids/blood ; Cell-Free Nucleic Acids/genetics ; Cell-Free Nucleic Acids/metabolism ; Cohort Studies ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Female ; GATA4 Transcription Factor/genetics ; GATA4 Transcription Factor/metabolism ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Pancreatic Neoplasms/blood ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; TEA Domain Transcription Factors ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Tumor Suppressor Proteins/genetics ; Tumor Suppressor Proteins/metabolism
Chemical Substances	Biomarkers, Tumor ; Cell-Free Nucleic Acids ; DNA-Binding Proteins ; GATA4 Transcription Factor ; GATA4 protein, human ; Homeodomain Proteins ; Nuclear Proteins ; TEA Domain Transcription Factors ; TEAD1 protein, human ; Transcription Factors ; Tumor Suppressor Proteins ; prospero-related homeobox 1 protein ; 5-hydroxymethylcytosine (1123-95-1) ; 5-Methylcytosine (6R795CQT4H)
Language	English
Publishing date	2020-10-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-020-18965-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Network crosstalk dynamically changes during neutrophil polarization.

Ku, Chin-Jen / Wang, Yanqin / Weiner, Orion D / Altschuler, Steven J / Wu, Lani F

Cell

2012 Volume 149, Issue 5, Page(s) 1073–1083

Abstract: How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or "crosstalk," among signaling modules involved in the ... ...

Abstract	How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or "crosstalk," among signaling modules involved in the cytoskeletal response of neutrophils to chemoattractant. We quantified the intensity and polarity of cytoskeletal marker proteins over time to characterize stereotyped cellular responses. Analyzing the effects of network disruptions revealed that, not only does crosstalk evolve rapidly during polarization, but also that intensity and polarity responses are influenced by different patterns of crosstalk. Interestingly, persistent crosstalk is arranged in a surprisingly simple circuit: a linear cascade from front to back to microtubules influences intensities, and a feed-forward network in the reverse direction influences polarity. Our approach provided a rational strategy for decomposing a complex, dynamically evolving signaling system and revealed evolving paths of causal influence that shape the neutrophil polarization response.
MeSH term(s)	Algorithms ; Cell Polarity ; Humans ; Kinetics ; Microtubules/metabolism ; Neutrophils/cytology ; Neutrophils/metabolism ; Phenotype ; Signal Transduction
Language	English
Publishing date	2012-05-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2012.03.044
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1167: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 58: Show issues

Order via subito

Details ▾

Article: ON IDENTIFYING INFORMATION FROM IMAGE-BASED SPATIAL POLARITY PHENOTYPES IN NEUTROPHILS.

Ku, Chin-Jen / Wang, Yanqin / Pavie, Benjamin / Altschuler, Steven J / Wu, Lani F

Proceedings. IEEE International Symposium on Biomedical Imaging

2010 Volume 14-17, Page(s) 1029–1032

Abstract: Cell polarity is involved in many biological functions such as development, wound healing and immune responses. In human neutrophils, polarization is characterized by the translocation of distinct sets of signaling molecules to opposite ends of the cell ... ...

Abstract	Cell polarity is involved in many biological functions such as development, wound healing and immune responses. In human neutrophils, polarization is characterized by the translocation of distinct sets of signaling molecules to opposite ends of the cell and the rapid rearrangement of cytoskeleton to initiate migration. While many image-based studies have described cellular morphology and the intensity level of polarity signaling molecules, systematic characterization of the spatial distribution of polarity signaling molecules has been lacking. Here we designed a collection of analytical features to quantify spatial phenotypes of polarity molecules. We compared our features to commonly used polarity readouts and found that they captured additional aspects of the polarization dynamics that were not contained in the existing features. Our work provides a starting point to identify informative features for the study of neutrophil polarization.
Language	English
Publishing date	2010-08-11
Publishing country	United States
Document type	Journal Article
ISSN	1945-7928
ISSN	1945-7928
DOI	10.1109/ISBI.2010.5490165
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Identifying network motifs that buffer front-to-back signaling in polarized neutrophils.

Wang, Yanqin / Ku, Chin-Jen / Zhang, Elizabeth R / Artyukhin, Alexander B / Weiner, Orion D / Wu, Lani F / Altschuler, Steven J

Cell reports

2013 Volume 3, Issue 5, Page(s) 1607–1616

Abstract: Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of ... ...

Abstract	Neutrophil polarity relies on local, mutual inhibition to segregate incompatible signaling circuits to the leading and trailing edges. Mutual inhibition alone should lead to cells having strong fronts and weak backs or vice versa. However, analysis of cell-to-cell variation in human neutrophils revealed that back polarity remains consistent despite changes in front strength. How is this buffering achieved? Pharmacological perturbations and mathematical modeling revealed a functional role for microtubules in buffering back polarity by mediating positive, long-range crosstalk from front to back; loss of microtubules inhibits buffering and results in anticorrelation between front and back signaling. Furthermore, a systematic, computational search of network topologies found that a long-range, positive front-to-back link is necessary for back buffering. Our studies suggest a design principle that can be employed by polarity networks: short-range mutual inhibition establishes distinct signaling regions, after which directed long-range activation insulates one region from variations in the other.
MeSH term(s)	Cell Movement ; Cell Polarity/physiology ; Humans ; Microtubules/metabolism ; Models, Theoretical ; Neutrophils/cytology ; Signal Transduction
Language	English
Publishing date	2013-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2013.04.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Patterns of basal signaling heterogeneity can distinguish cellular populations with different drug sensitivities.

Singh, Dinesh Kumar / Ku, Chin-Jen / Wichaidit, Chonlarat / Steininger, Robert J / Wu, Lani F / Altschuler, Steven J

Molecular systems biology

2010 Volume 6, Page(s) 369

Abstract: Phenotypic heterogeneity has been widely observed in cellular populations. However, the extent to which heterogeneity contains biologically or clinically important information is not well understood. Here, we investigated whether patterns of basal ... ...

Abstract	Phenotypic heterogeneity has been widely observed in cellular populations. However, the extent to which heterogeneity contains biologically or clinically important information is not well understood. Here, we investigated whether patterns of basal signaling heterogeneity, in untreated cancer cell populations, could distinguish cellular populations with different drug sensitivities. We modeled cellular heterogeneity as a mixture of stereotyped signaling states, identified based on colocalization patterns of activated signaling molecules from microscopy images. We found that patterns of heterogeneity could be used to separate the most sensitive and resistant populations to paclitaxel within a set of H460 lung cancer clones and within the NCI-60 panel of cancer cell lines, but not for a set of less heterogeneous, immortalized noncancer human bronchial epithelial cell (HBEC) clones. Our results suggest that patterns of signaling heterogeneity, characterized as ensembles of a small number of distinct phenotypic states, can reveal functional differences among cellular populations.
MeSH term(s)	Biomarkers, Tumor/genetics ; Cell Line, Transformed ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics ; Genetic Heterogeneity ; Humans ; Intracellular Signaling Peptides and Proteins/genetics ; Microscopy, Fluorescence ; Multivariate Analysis ; Neoplasms/drug therapy ; Neoplasms/genetics ; Neoplasms/pathology ; Paclitaxel/pharmacology ; Signal Transduction/genetics ; Systems Biology
Chemical Substances	Biomarkers, Tumor ; Intracellular Signaling Peptides and Proteins ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2010-05-11
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1744-4292
ISSN (online)	1744-4292
DOI	10.1038/msb.2010.22
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: Network Crosstalk Dynamically Changes during Neutrophil Polarization

Ku, Chin-Jen / Wang, Yanqin / Weiner, Orion D. / Altschuler, Steven J. / Wu, Lani F.

Cell

Volume v. 149,, Issue no. 5

Abstract: How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or “crosstalk,” among signaling modules involved in the ... ...

Abstract	How complex signaling networks shape highly coordinated, multistep cellular responses is poorly understood. Here, we made use of a network-perturbation approach to investigate causal influences, or “crosstalk,” among signaling modules involved in the cytoskeletal response of neutrophils to chemoattractant. We quantified the intensity and polarity of cytoskeletal marker proteins over time to characterize stereotyped cellular responses. Analyzing the effects of network disruptions revealed that, not only does crosstalk evolve rapidly during polarization, but also that intensity and polarity responses are influenced by different patterns of crosstalk. Interestingly, persistent crosstalk is arranged in a surprisingly simple circuit: a linear cascade from front to back to microtubules influences intensities, and a feed-forward network in the reverse direction influences polarity. Our approach provided a rational strategy for decomposing a complex, dynamically evolving signaling system and revealed evolving paths of causal influence that shape the neutrophil polarization response.
Keywords	polarization ; microtubules ; chemoattractants ; neutrophils ; proteins
Language	English
Document type	Article
ISSN	0092-8674
Database	AGRIS - International Information System for the Agricultural Sciences and Technology

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

To top

Your last searches

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

Inter-library loan at ZB MED