TY  - JOUR
A1  - Zhang, Gong
A1  - Fedyunin, Ivan
A1  - Kirchner, Sebastian
A1  - Xiao, Chuanle
A1  - Valleriani, Angelo
A1  - Ignatova, Zoya
T1  - FANSe: an accurate algorithm for quantitative mapping of large scale sequencing reads
JF  - Nucleic acids research
N2  - The most crucial step in data processing from high-throughput sequencing applications is the accurate and sensitive alignment of the sequencing reads to reference genomes or transcriptomes. The accurate detection of insertions and deletions (indels) and errors introduced by the sequencing platform or by misreading of modified nucleotides is essential for the quantitative processing of the RNA-based sequencing (RNA-Seq) datasets and for the identification of genetic variations and modification patterns. We developed a new, fast and accurate algorithm for nucleic acid sequence analysis, FANSe, with adjustable mismatch allowance settings and ability to handle indels to accurately and quantitatively map millions of reads to small or large reference genomes. It is a seed-based algorithm which uses the whole read information for mapping and high sensitivity and low ambiguity are achieved by using short and non-overlapping reads. Furthermore, FANSe uses hotspot score to prioritize the processing of highly possible matches and implements modified Smith-Watermann refinement with reduced scoring matrix to accelerate the calculation without compromising its sensitivity. The FANSe algorithm stably processes datasets from various sequencing platforms, masked or unmasked and small or large genomes. It shows a remarkable coverage of low-abundance mRNAs which is important for quantitative processing of RNA-Seq datasets.
Y1  - 2012
U6  - https://doi.org/10.1093/nar/gks196
SN  - 0305-1048
VL  - 40
IS  - 11
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Hinz, Justyna
A1  - Lehnhardt, Lothar
A1  - Zakrzewski, Silke
A1  - Zhang, Gong
A1  - Ignatova, Zoya
T1  - Polyglutamine expansion alters the dynamics and molecular architecture of aggregates in dentatorubropallidoluysian atrophy
JF  - The journal of biological chemistry
N2  - Preferential accumulation of mutant proteins in the nucleus has been suggested to be the molecular culprit that confers cellular toxicity in the neurodegenerative disorders caused by polyglutamine (polyQ) expansion. Here, we use dynamic imaging approaches, orthogonal cross-seeding, and composition analysis to examine the dynamics and structure of nuclear and cytoplasmic inclusions of atrophin-1, implicated in dentatorubropallidoluysian atrophy, a polyQ-based disease with complex clinical features. Our results reveal a large heterogeneity in the dynamics of the nuclear inclusions compared with the compact and immobile cytoplasmic aggregates. At least two types of inclusions of expanded atrophin-1 with different mobility of the molecular species and ability to exchange with the surrounding monomer pool coexist in the nucleus. Intriguingly, the enrichment of nuclear inclusions with slow dynamics parallels changes in the aggregate core architecture that are dominated by the polyQ stretch. We propose that the observed complexity in the dynamics of the nuclear inclusions provides a molecular explanation for the enhanced cellular toxicity of the nuclear aggregates in polyQ-based neurodegeneration.
Y1  - 2012
U6  - https://doi.org/10.1074/jbc.M111.318915
SN  - 0021-9258
VL  - 287
IS  - 3
SP  - 2068
EP  - 2078
PB  - American Society for Biochemistry and Molecular Biology
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Fedyunin, Ivan
A1  - Lehnhardt, Lothar
A1  - Böhmer, Nadine
A1  - Kaufmann, Paul
A1  - Zhang, Gong
A1  - Ignatova, Zoya
T1  - tRNA concentration fine tunes protein solubility
JF  - FEBS letters : the journal for rapid publication of short reports in molecular biosciences
N2  - Clusters of codons pairing to low-abundance tRNAs synchronize the translation with co-translational folding of single domains in multidomain proteins. Although proven with some examples, the impact of the ribosomal speed on the folding and solubility on a global, cell-wide level remains elusive. Here we show that upregulation of three low-abundance tRNAs in Escherichia coil increased the aggregation propensity of several cellular proteins as a result of an accelerated elongation rate. Intriguingly, alterations in the concentration of the natural tRNA pool compromised the solubility of various chaperones consequently rendering the solubility of some chaperone-dependent proteins.
KW  - Protein translation
KW  - Protein misfolding
KW  - tRNA
KW  - E. coli
Y1  - 2012
U6  - https://doi.org/10.1016/j.febslet.2012.07.012
SN  - 0014-5793
VL  - 586
IS  - 19
SP  - 3336
EP  - 3340
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Fedyunin, Ivan
A1  - Lehnhardt, Lothar
A1  - Böhmer, Nadine
A1  - Kaufmann, Paul
A1  - Zhang, Gong
A1  - Ignatov, Zoya
T1  - tRNA concentration fine tunes protein solubility
Y1  - 2012
UR  - http://www.sciencedirect.com/science/article/pii/S0014579312005807
ER  -