Sense and Nonsense of Pathway Analysis Software in Proteomics

Müller, Thorsten; Schrötter, Andreas; Looße, Christina; Helling, Stefan; Stephan, Christian; Ahrens, Maike; Uszkoreit, Julian; Eisenacher, Martin; Meyer, Helmut E.; Marcus, Katrin

doi:10.1021/pr200654k

Cited by 41 publications

(33 citation statements)

References 33 publications

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“…Processed spectral counts (PSC) based on spectral and peptide counts were calculated as described previously (16,18) and subsequently used as basis for label-free quantification. In brief, PSC calculation was performed by summing up all spectral counts belonging to the respective protein.…”

Section: Methodsmentioning

confidence: 99%

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

Schrötter

Pfeiffer

Magraoui

et al. 2012

Molecular & Cellular Proteomics

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The amyloid precursor protein (APP)1 is a species-conserved integral membrane protein, which is expressed in many tissues. A role for APP has been suggested in neurite outgrowth and synaptogenesis, protein trafficking along axons, cell adhesion, calcium metabolism, and signal transduction (reviewed in (1, 2)). During its life cycle, APP is cleaved into various fragments mediating different functions. Next to A␤ (and the p3 fragment), extracellular soluble fragments (sAPP␣ or sAPP␤), and intracellular fragments (APP intracellular domain, AICD) are generated. After sequential ␤-and

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Section: Methodsmentioning

confidence: 99%

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

Schrötter

Pfeiffer

Magraoui

et al. 2012

Molecular & Cellular Proteomics

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“…A spectral index (SI) based on spectral and peptide counts was calculated as described previously (22,23) and subsequently used as basis for label-free quantification. In brief, spectral index calculation was performed by summing up all spectral counts belonging to the respective protein.…”

Section: Detection Of Aggregates By Immunofluorescence Staining and La-mentioning

confidence: 99%

“…binding partners of the mutated proteins. Here, we applied a workflow consisting of laser microdissection and label-free spectral count-based proteomics not restricted to pre-selected proteins (22,23,35) with the ultimate goal to get new insights into aggregate composition in filaminopathy muscle samples. To our knowledge, it was the first time that this strategy was performed in immunostained skeletal muscle sections.…”

Section: Fig 1 Workflow For the Identification Of Mfm Biomarkers Bymentioning

confidence: 99%

A Combined Laser Microdissection and Mass Spectrometry Approach Reveals New Disease Relevant Proteins Accumulating in Aggregates of Filaminopathy Patients

Kley

Maerkens

Leber

et al. 2013

Molecular & Cellular Proteomics

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Filaminopathy is a subtype of myofibrillar myopathy caused by mutations in FLNC, the gene encoding filamin C, and histologically characterized by pathologic accumulation of several proteins within skeletal muscle fibers. With the aim to get new insights in aggregate composition, we collected aggregates and control tissue from skeletal muscle biopsies of six myofibrillar myopathy patients harboring three different FLNC mutations by laser microdissection and analyzed the samples by a label-free mass spectrometry approach. A total of 390 proteins were identified, and 31 of those showed significantly higher spectral indices in aggregates compared with patient controls with a ratio >1.8. These proteins included filamin C, other known myofibrillar myopathy associated proteins, and a striking number of filamin C binding partners. Across the patients the patterns were extremely homogeneous. Xin actin-binding repeat containing protein 2, heat shock protein 27, nebulin-related-anchoring protein, and Rab35 could be verified as new filaminopathy biomarker candidates. In addition, further experiments identified heat shock protein 27 and Xin actin-binding repeat containing protein 2 as novel filamin C interaction partners and we could show that Xin actin-binding repeat containing protein 2 and the known interaction partner Xin actinbinding repeat containing protein 1 simultaneously associate with filamin C. Ten proteins showed significant lower spectral indices in aggregate samples compared with patient controls (ratio <0.56) including M-band proteins myomesin-1 and myomesin-2. Proteomic findings were consistent with previous and novel immunolocalization data. Our findings suggest that aggregates in filaminopathy have a largely organized structure of proteins also interacting under physiological conditions. Different filamin C mutations seem to lead to almost identical aggregate compositions. The finding that filamin C was detected as highly abundant protein in aggregates in filaminopathy indicates that our proteomic approach may be suitable to identify new candidate genes among the many MFM patients with so far unknown mutation. Molecular & Cellular Proteomics

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“…4. Finally, we have developed complex software and computers with huge memories and lightning-fast computational capabilities to actually model how all the biochemical and signaling pathways interact and coordinately function (on average) [10]. Such computers now control robots that can perform complicated surgical procedures more precisely than can humans.…”

Section: Body Managementmentioning

confidence: 99%

Body Management: Mesenchymal Stem Cells Control the Internal Regenerator

Caplan

Hariri²

2015

Stem Cells Translational Medicine

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SUMMARYIt has been assumed that adult tissues cannot regenerate themselves. With the current understanding that every adult tissue has its own intrinsic progenitor or stem cell, it is now clear that almost all tissues have regenerative potential partially related to their innate turnover dynamics. Moreover, it appears that a separate class of local cells originating as perivascular cells appears to provide regulatory oversight for localized tissue regeneration. The management of this regeneration oversight has a profound influence on the use of specific cells for cell therapies as a health care delivery tool set. The multipotent mesenchymal stem cell (MSC), now renamed the medicinal signaling cell, predominantly arises from pericytes released from broken and inflamed blood vessels and appears to function as both an immunomodulatory and a regeneration mediator. MSCs are being tested for their management capabilities to produce therapeutic outcomes in more than 480 clinical trials for a wide range of clinical conditions. Local MSCs function by managing the body's primary repair and regeneration activities. Supplemental MSCs can be provided from either endogenous or exogenous sources of either allogeneic or autologous origin. This MSC-based therapy has the potential to change how health care is delivered. These medicinal cells are capable of sensing their surroundings. Also, by using its complex signaling circuitry, these cells organize site-specific regenerative responses as if these therapeutic cells were well-programmed modern computers. Given these facts, it appears that we are entering a new age of cellular medicine. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:695-701 SIGNIFICANCEThis report is a perspective from an active scientist and an active entrepreneur and commercial leader. It is neither a comprehensive review nor a narrowly focused treatise. The broad themes and the analogy to the working component of a computer and that of a cell are meant to draw several important scientific principles and health care themes together into the thesis that regenerative medicine is a constant throughout life and its management is the next frontier of health care. Mesenchymal stem cells are used as the central connection in the broad theme, not as multipotent progenitors but rather as an important control element in the natural local regeneration process.

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Sense and Nonsense of Pathway Analysis Software in Proteomics

Cited by 41 publications

References 33 publications

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

The Amyloid Precursor Protein (APP) Family Members are Key Players in S-adenosylmethionine Formation by MAT2A and Modify BACE1 and PSEN1 Gene Expression-Relevance for Alzheimer's Disease

A Combined Laser Microdissection and Mass Spectrometry Approach Reveals New Disease Relevant Proteins Accumulating in Aggregates of Filaminopathy Patients

Body Management: Mesenchymal Stem Cells Control the Internal Regenerator

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