To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88 , CARD11 , EZH2 , and CREBBP . We also identified somatic mutations in genes for which a functional role in DLBCL has not been previously suspected. These genes include MEF2B , MLL2 , BTG1 , GNA13 , ACTB , P2RY8 , PCLO , and TNFRSF14 . Further, we show that BCL2 mutations commonly occur in patients with BCL2 / IgH rearrangements as a result of somatic hypermutation normally occurring at the IgH locus. The BCL2 point mutations are primarily synonymous, and likely caused by activation-induced cytidine deaminase–mediated somatic hypermutation, as shown by comprehensive analysis of enrichment of mutations in WRCY target motifs. Those nonsynonymous mutations that are observed tend to be found outside of the functionally important BH domains of the protein, suggesting that strong negative selection against BCL2 loss-of-function mutations is at play. Last, by using an algorithm designed to identify likely functionally relevant but infrequent mutations, we identify KRAS , BRAF , and NOTCH1 as likely drivers of DLBCL pathogenesis in some patients. Our data provide an unbiased view of the landscape of mutations in DLBCL, and this in turn may point toward new therapeutic strategies for the disease.

Periodontitis is a common inflammatory disease of infectious origins that often evolves into a chronic condition. Aside from its importance as a stomatologic ailment, chronic periodontitis has gained relevance since it has been shown that it can develop into a systemic condition characterized by unresolved hyper-inflammation, disruption of the innate and adaptive immune system, dysbiosis of the oral, gut and other location's microbiota and other system-wide alterations that may cause, coexist or aggravate other health issues associated to elevated morbi-mortality. The relationships between the infectious, immune, inflammatory, and systemic features of periodontitis and its many related diseases are far from being fully understood and are indeed still debated. However, to date, a large body of evidence on the different biological, clinical, and policy-enabling sources of information, is available. The aim of the present work is to summarize many of these sources of information and contextualize them under a systemic inflammation framework that may set the basis to an integral vision, useful for basic, clinical, and therapeutic goals.

Mexico is developing the basis for genomic medicine to improve healthcare of its population. The extensive study of genetic diversity and linkage disequilibrium structure of different populations has made it possible to develop tagging and imputation strategies to comprehensively analyze common genetic variation in association studies of complex diseases. We assessed the benefit of a Mexican haplotype map to improve identification of genes related to common diseases in the Mexican population. We evaluated genetic diversity, linkage disequilibrium patterns, and extent of haplotype sharing using genomewide data from Mexican Mestizos from regions with different histories of admixture and particular population dynamics. Ancestry was evaluated by including 1 Mexican Amerindian group and data from the HapMap. Our results provide evidence of genetic differences between Mexican subpopulations that should be considered in the design and analysis of association studies of complex diseases. In addition, these results support the notion that a haplotype map of the Mexican Mestizo population can reduce the number of tag SNPs required to characterize common genetic variation in this population. This is one of the first genomewide genotyping efforts of a recently admixed population in Latin America.

Pathway analysis is a set of widely used tools for research in life sciences intended to give meaning to high-throughput biological data. The methodology of these tools settles in the gathering and usage of knowledge that comprise biomolecular functioning, coupled with statistical testing and other algorithms. Despite their wide employment, pathway analysis foundations and overall background may not be fully understood, leading to misinterpretation of analysis results. This review attempts to comprise the fundamental knowledge to take into consideration when using pathway analysis as a hypothesis generation tool. We discuss the key elements that are part of these methodologies, their capabilities and current deficiencies. We also present an overview of current and all-time popular methods, highlighting different classes across them. In doing so, we show the exploding diversity of methods that pathway analysis encompasses, point out commonly overlooked caveats, and direct attention to a potential new class of methods that attempt to zoom the analysis scope to the sample scale.

A main goal of Precision Medicine is that of incorporating and integrating the vast corpora on different databases about the molecular and environmental origins of disease, into analytic frameworks, allowing the development of individualized, context-dependent diagnostics, and therapeutic approaches. In this regard, artificial intelligence and machine learning approaches can be used to build analytical models of complex disease aimed at prediction of personalized health conditions and outcomes. Such models must handle the wide heterogeneity of individuals in both their genetic predisposition and their social and environmental determinants. Computational approaches to medicine need to be able to efficiently manage, visualize and integrate, large datasets combining structure, and unstructured formats. This needs to be done while constrained by different levels of confidentiality, ideally doing so within a unified analytical architecture. Efficient data integration and management is key to the successful application of computational intelligence approaches to medicine. A number of challenges arise in the design of successful designs to medical data analytics under currently demanding conditions of performance in personalized medicine, while also subject to time, computational power, and bioethical constraints. Here, we will review some of these constraints and discuss possible avenues to overcome current challenges.

Cancer is the quintessential complex disease. As technologies evolve faster each day, we are able to quantify the different layers of biological elements that contribute to the emergence and development of malignancies. In this multi-omics context, the use of integrative approaches is mandatory in order to gain further insights on oncological phenomena, and to move forward toward the precision medicine paradigm. In this review, we will focus on computational oncology as an integrative discipline that incorporates knowledge from the mathematical, physical, and computational fields to further the biomedical understanding of cancer. We will discuss the current roles of computation in oncology in the context of multi-omic technologies, which include: data acquisition and processing; data management in the clinical and research settings; classification, diagnosis, and prognosis; and the development of models in the research setting, including their use for therapeutic target identification. We will discuss the machine learning and network approaches as two of the most promising emerging paradigms, in computational oncology. These approaches provide a foundation on how to integrate different layers of biological description into coherent frameworks that allow advances both in the basic and clinical settings.