BiC2PAM: constraint-guided biclustering for biological data analysis with domain knowledge

Background

Biclustering has been largely used in biological data analysis, enabling the discovery of putative functional modules from omic and network data. Despite the recognized importance of incorporating domain knowledge to guide biclustering and guarantee a focus on relevant and non-trivial biclusters, this possibility has not yet been comprehensively addressed. This results from the fact that the majority of existing algorithms are only able to deliver sub-optimal solutions with restrictive assumptions on the structure, coherency and quality of biclustering solutions, thus preventing the up-front satisfaction of knowledge-driven constraints. Interestingly, in recent years, a clearer understanding of the synergies between pattern mining and biclustering gave rise to a new class of algorithms, termed as pattern-based biclustering algorithms. These algorithms, able to efficiently discover flexible biclustering solutions with optimality guarantees, are thus positioned as good candidates for knowledge incorporation. In this context, this work aims to bridge the current lack of solid views on the use of background knowledge to guide (pattern-based) biclustering tasks.

Methods

This work extends (pattern-based) biclustering algorithms to guarantee the satisfiability of constraints derived from background knowledge and to effectively explore efficiency gains from their incorporation. In this context, we first show the relevance of constraints with succinct, (anti-)monotone and convertible properties for the analysis of expression data and biological networks. We further show how pattern-based biclustering algorithms can be adapted to effectively prune of the search space in the presence of such constraints, as well as be guided in the presence of biological annotations. Relying on these contributions, we propose BiClustering with Constraints using PAttern Mining (BiC2PAM), an extension of BicPAM and BicNET biclustering algorithms.

Results

Experimental results on biological data demonstrate the importance of incorporating knowledge within biclustering to foster efficiency and enable the discovery of non-trivial biclusters with heightened biological relevance.

Conclusions

This work provides the first comprehensive view and sound algorithm for biclustering biological data with constraints derived from user expectations, knowledge repositories and/or literature.

     

Oxalate transfer across the membranes of sarcoplasmic reticulum during the uptake of Ca++

The kinetic profile of Ca++ uptake in the presence of oxalate is biphasic. An initial phase independent on oxalate is followed by an oxalate-dependent phase delayed in time. The ionophore X-537A only abolishes the net Ca++ uptake if added before the onset of the oxalate phase. However, during this phase, X-537A suddenly releases an amount of Ca++ similar in quantity to that released in the initial phase. The delay of the oxalate-dependent phase is a function of pH. At pH of about 5.5, the oxalate phase and simultaneous calcium oxalate precipitation would theoretically start at the beginning, with no delay. Ejection of protons during Ca++ uptake is strongly depressed by oxalate, but not by other organic anions which do not trap Ca++. It is suggested that oxalate is transferred to the inside of the vesicles as a monoprotonated species at expense of protons ejected by the Ca++-pump during the uptake of Ca++.     

Proton gradient formation during transport of Ca2+ by sarcoplasmic reticulum.

(i) Hydrolysis of ATP by leaky sarcoplasmic reticulum vesicles generates less protons than does hydrolysis of intact membranes. Even under conditions where the hydrolysis of ATP does not produce protons (pH 6.0) intact membranes still release protons during Ca²⁺ uptake. (ii) The fluorescence of 9-amino-6-chloro-2-methoxyacridine increases suddenly after triggering the transport of Ca²⁺ and declines when Ca²⁺ has been accumulated by the vesicles. The behavior of atebrin is opposite to that of 9-aminoacridine. The rate of the fluorescence change is much higher than the rate of Ca²⁺ translocation, and the maximum fluorescence does not depend on the amount of Ca²⁺ accumulated. (iii) The fluorescence of 3,3′-dipentyloxadicarbocyanine increases at a rate similar to that of Ca²⁺ uptake and declines when 70–80% of Ca²⁺ has been accumulated. (iv) The results suggest quite clearly that a proton gradient, which forms rapidly, is the motive force for sustaining the Ca²⁺ transport. A transient transmembrane electrical potential develops as a secondary effect during Ca²⁺ translocation.     

Are three colonies of Neostromboceros albicomus,a candidate biological control agent for Lygodium microphyllum,the same host biotype?

Three colonies of Neostromboceros albicomus, a candidate biological control agent of Lygodium microphyllum, were barcoded using the D2 expansion domain, to determine which of two biotypes they represented. The first colony, collected in 2005 and 2007, was used for the initial host range testing. Colonies collected in 2012 and 2014 are currently being used to finalise this testing. All three colonies were collected in Trat Province, Thailand and all three populations show identical sequences to the N. albicomus biotype which prefers L. microphyllum as its host plant. The N. albicomus biotype that uses L. flexuosum as its host plant differs by a single nucleotide, a difference which may reflect cryptic speciation.     

Prion protein gene polymorphisms in sheep in the state of Paraná, Brazil

To determine the polymorphisms of the prion protein gene in sheep from the state of Paraná, Brazil, 323 animals of meat breeds (Suffolk, Hampshire Down, Texel, Ile de France, Dorper, Dorset, Santa Inês and crossbreds) were genotyped by restriction fragment length polymorphism (RFLP) analysis. The most frequent allele was ARQ, with a frequency of 0.61, followed by ARR (0.30). VRQ and AHQ alleles were present at very low frequencies (0.13 and 0.05 respectively), and the ARH allele was not found. Seven genotypes were identified (ARR/ARR, ARR/ARQ, ARQ/ARQ, ARR/VRQ, ARR/AHQ, ARQ/VRQ and ARQ/AHQ), of which ARQ/ARQ was the most frequent (0.41). The Santa Inês breed and crossbred animals showed the highest genotypic variability.     

Rubidium marking reveals different patterns of movement in four ground beetle species (Col., Carabidae) between adjacent alfalfa and maize

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Effect of short-chain primary alcohols on fluidity and activity of sarcoplasmic reticulum membranes

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