Loss of Conservation of Graph Centralities in Reverse-engineered Transcriptional Regulatory Networks

Weishaupt, HolgerUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi,Uppsala Univ, Dept Immunol Genet & Pathol, Sci Life Lab, Dag Hammarskjoldsvag 20, S-75185 Uppsala, Sweden. (författare)

Graph centralities are commonly used to identify and prioritize disease genes in transcriptional regulatory networks. Studies on small networks of experimentally validated protein-protein interactions underpin the general validity of this approach and extensions of such findings have recently been proposed for networks inferred from gene expression data. However, it is largely unknown how well gene centralities are preserved between the underlying biological interactions and the networks inferred from gene expression data. Specifically, while previous studies have evaluated the performance of inference methods on synthetic gene expression, it has not been established how the choice of inference method affects individual centralities in the network. Here, we compare two gene centrality measures between reference networks and networks inferred from corresponding simulated gene expression data, using a number of commonly used network inference methods. The results indicate that the centrality of genes is only moderately conserved for all of the inference methods used. In conclusion, caution should be exercised when inspecting centralities in reverse-engineered networks and further work will be required to establish the use of such networks for prioritizing disease genes.

Johansson, PatrikUppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)patjo183 (författare)
Engström, Christopher,1987-Mälardalens högskola,Utbildningsvetenskap och Matematik,Mälardalen Univ, Sch Educ Culture & Commun UKK, Div Appl Math, Box 883, S-72123 Vasteras, Sweden.(Swepub:mdh)cem02 (författare)
Nelander, SvenUppsala universitet,Science for Life Laboratory, SciLifeLab,Neuroonkologi(Swepub:uu)svene843 (författare)
Silvestrov, Sergei,1970-Mälardalens högskola,Utbildningsvetenskap och Matematik,Mälardalen Univ, Sch Educ Culture & Commun UKK, Div Appl Math, Box 883, S-72123 Vasteras, Sweden.(Swepub:mdh)ssv01 (författare)
Swartling, Fredrik J.,1975-Uppsala universitet,Neuroonkologi,Science for Life Laboratory, SciLifeLab(Swepub:uu)fredjoha (författare)
Uppsala universitetScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Ingår i:Methodology and Computing in Applied Probability: Springer19:4, s. 1095-11051387-58411573-7713

Av författaren/redakt...: Weishaupt, Holge ...; Johansson, Patri ...; Engström, Christ ...; Nelander, Sven; Silvestrov, Serg ...; Swartling, Fredr ...

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