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  - Kirchner, Sebastian
A1  - Ignatova, Zoya
T1  - Emerging roles of tRNA in adaptive translation, signalling dynamics and disease
JF  - Nature reviews
N2  - tRNAs, nexus molecules between mRNAs and proteins, have a central role in translation. Recent discoveries have revealed unprecedented complexity of tRNA biosynthesis, modification patterns, regulation and function. In this Review, we present emerging concepts regarding how tRNA abundance is dynamically regulated and how tRNAs (and their nucleolytic fragments) are centrally involved in stress signalling and adaptive translation, operating across a wide range of timescales. Mutations in tRNAs or in genes affecting tRNA biogenesis are also linked to complex human diseases with surprising heterogeneity in tissue vulnerability, and we highlight cell-specific aspects that modulate the disease penetrance of tRNA-based pathologies.
Y1  - 2015
U6  - https://doi.org/10.1038/nrg3861
SN  - 1471-0056
SN  - 1471-0064
VL  - 16
IS  - 2
SP  - 98
EP  - 112
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Kirchner, Sebastian
A1  - Cai, Zhiwei
A1  - Rauscher, Robert
A1  - Kastelic, Nicolai
A1  - Anding, Melanie
A1  - Czech, Andreas
A1  - Kleizen, Bertrand
A1  - Ostedgaard, Lynda S.
A1  - Braakman, Ineke
A1  - Sheppard, David N.
A1  - Ignatova, Zoya
T1  - Alteration of protein function by a silent polymorphism linked to tRNA abundance
JF  - PLoS biology
N2  - Synonymous single nucleotide polymorphisms (sSNPs) are considered neutral for protein function, as by definition they exchange only codons, not amino acids. We identified an sSNP that modifies the local translation speed of the cystic fibrosis transmembrane conductance regulator (CFTR), leading to detrimental changes to protein stability and function. This sSNP introduces a codon pairing to a low-abundance tRNA that is particularly rare in human bronchial epithelia, but not in other human tissues, suggesting tissue-specific effects of this sSNP. Up-regulation of the tRNA cognate to the mutated codon counteracts the effects of the sSNP and rescues protein conformation and function. Our results highlight the wide-ranging impact of sSNPs, which invert the programmed local speed of mRNA translation and provide direct evidence for the central role of cellular tRNA levels in mediating the actions of sSNPs in a tissue-specific manner.
Y1  - 2017
U6  - https://doi.org/10.1371/journal.pbio.2000779
SN  - 1545-7885
VL  - 15
PB  - PLoS
CY  - San Fransisco
ER  -