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- 2019
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Tidskriftsartikel (refereegranskat)
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- Khan, Yusuf, et al.
(författare)
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Increased biological relevance of transcriptome analyses in human skeletal muscle using a model-specific pipeline.
- 2020
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Ingår i: BMC Bioinformatics. - : BioMed Central. - 1471-2105. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Human skeletal muscle responds to weight-bearing exercise with significant inter-individual differences. Investigation of transcriptome responses could improve our understanding of this variation. However, this requires bioinformatic pipelines to be established and evaluated in study-specific contexts. Skeletal muscle subjected to mechanical stress, such as through resistance training (RT), accumulates RNA due to increased ribosomal biogenesis. When a fixed amount of total-RNA is used for RNA-seq library preparations, mRNA counts are thus assessed in different amounts of tissue, potentially invalidating subsequent conclusions. The purpose of this study was to establish a bioinformatic pipeline specific for analysis of RNA-seq data from skeletal muscles, to explore the effects of different normalization strategies and to identify genes responding to RT in a volume-dependent manner (moderate vs. low volume). To this end, we analyzed RNA-seq data derived from a twelve-week RT intervention, wherein 25 participants performed both low- and moderate-volume leg RT, allocated to the two legs in a randomized manner. Bilateral muscle biopsies were sampled from m. vastus lateralis before and after the intervention, as well as before and after the fifth training session (Week 2).RESULT: Bioinformatic tools were selected based on read quality, observed gene counts, methodological variation between paired observations, and correlations between mRNA abundance and protein expression of myosin heavy chain family proteins. Different normalization strategies were compared to account for global changes in RNA to tissue ratio. After accounting for the amounts of muscle tissue used in library preparation, global mRNA expression increased by 43-53%. At Week 2, this was accompanied by dose-dependent increases for 21 genes in rested-state muscle, most of which were related to the extracellular matrix. In contrast, at Week 12, no readily explainable dose-dependencies were observed. Instead, traditional normalization and non-normalized models resulted in counterintuitive reverse dose-dependency for many genes. Overall, training led to robust transcriptome changes, with the number of differentially expressed genes ranging from 603 to 5110, varying with time point and normalization strategy.CONCLUSION: Optimized selection of bioinformatic tools increases the biological relevance of transcriptome analyses from resistance-trained skeletal muscle. Moreover, normalization procedures need to account for global changes in rRNA and mRNA abundance.
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- Stathis, Dimitrios, 1989-, et al.
(författare)
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Approximate Computing Applied to Bacterial Genome Identification using Self-Organizing Maps
- 2019
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Ingår i: 2019 IEEE Computer Society Annual Symposium On VLSI (ISVLSI 2019). - : IEEE. - 9781728133911 ; , s. 562-569
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Konferensbidrag (refereegranskat)abstract
- In this paper we explore the design space of a self-organizing map (SOM) used for rapid and accurate identification of bacterial genomes. This is an important health care problem because even in Europe, 70% of prescriptions for antibiotics is wrong. The SOM is trained on Next Generation Sequencing (NGS) data and is able to identify the exact strain of bacteria. This is in contrast to conventional methods that require genome assembly to identify the bacterial strain. SOM has been implemented as an synchoros VLSI design and shown to have 3-4 orders better computational efficiency compared to GPUs. To further lower the energy consumption, we exploit the robustness of SOM by successively lowering the resolution to gain further improvements in efficiency and lower the implementation cost without substantially sacrificing the accuracy. We do an in depth analysis of the reduction in resolution vs. loss in accuracy as the basis for designing a system with the lowest cost and acceptable accuracy using NGS data from samples containing multiple bacteria from the labs of one of the co-authors. The objective of this method is to design a bacterial recognition system for battery operated clinical use where the area, power and performance are of critical importance. We demonstrate that with 39% loss in accuracy in 12 hits and 1% in 16 bit representation can yield significant savings in energy and area.
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