A Process Calculus for Molecular Interaction Maps

We present the MIM calculus, a modeling formalism with a strong biological basis, which provides biologically-meaningful operators for representing the interaction capabilities of molecular species. The operators of the calculus are inspired by the reaction symbols used in Molecular Interaction Maps (MIMs), a diagrammatic notation used by biologists. Models of the calculus can be easily derived from MIM diagrams, for which an unambiguous and executable interpretation is thus obtained. We give a formal definition of the syntax and semantics of the MIM calculus, and we study properties of the formalism. A case study is also presented to show the use of the calculus for modeling biomolecular networks.Comment: 15 pages; 8 figures; To be published on EPTCS, proceedings of MeCBIC 200

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

A Core Modeling Language for the Working Molecular Biologist

this paper is to demonstrate this with a side-by-side comparison of standard biological subsystems described in natural language and their precise and concise rendering in the formalism. All examples are taken from the cell cycle control reaction network after Kohn's revered molecular maps [Koh99

PHÂN LẬP VÀ ĐỊNH TÍNH METALLOTHIONEIN TRONG TIỂU CẦU MÁU NGƯỜI

Metallothionein (MT) là một nhóm protein mang kim loại, có trọng lượng phân tử thấp, giàu cystein.  Chúng hiện diện trong động vật, thực vật bậc cao, vi sinh vật chân hạch và một số vi sinh vật sơ hạch.  MT từ tiểu cầu máu được trích bằng cách phá vỡ tế bào, sau đó MT được tách dựa trên sự khác biệt kích thước phân tử bằng phương pháp sắc ký thấm (gel permeation chromatography), sự hiện diện của MT được xác định thông qua phương pháp điện di và phương pháp thấm miễn dịch (immunoblotting- Western blotting).  Dung dịch protein chứa MT được tinh sạch bằng phương pháp sắc ký ái lực ?ngược? (negative affinity chromatography) để loại bỏ protein liên kết acid béo (Fatty acids binding proteins ? FABP), một nhóm protein có trọng lượng phân tử thấp hiện diện cùng với MT sau khi qua sắc ký thấm.  Dạng đồng đẳng (iso-form) MT được xác định bằng phương pháp sắc ký trao đổi ion (ion exchange chromatography), kết quả cho thấy MT hiện diện trong tiểu cầu máu người là đồng đẳng MT-0.

Modeling and Querying Biomolecular Interaction Networks

We introduce a formalism to represent and analyze protein-protein and protein-DNA interaction networks. We illustrate the expressivity of this language, by proposing a formal counterpart of Kohn's compilation on the mammalian cell cycle control. This e#ectively turns an otherwise static knowledge into a discrete transition system incorporating a qualitative description of the dynamics. We then propose to use the Computation Tree Logic CTL as a query language for querying the possible behaviours of the system. We provide examples of biologically relevant queries expressed in CTL about the mammalian cell cycle control and show the e#ectiveness of symbolic model checking tools to evaluate CTL queries in this context

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient