Human Genome Research Articles

Limits of Interference into the Human Genome

Introduction: The use of advances in genomics in practical medicine can positively affect the quality of services in the healthcare sector, as well as the results of applied medical research. Objectives: The purpose of the article is to research regulatory and scientific approaches to the concept of the human genome as an object of legal relations, as well as to determine the limits of interference into a human being’s genomic integrity. Materials and methods: Regarding the chosen subject matter of research, the author while preparing the scientific article has used materials of international regulatory legal acts, Ukrainian and foreign legal literature. To achieve the set aim, the author has used general scientific and special methods of scientific cognition. These methods combined with the scientific principles of objectivity, scientificity and reasonableness, have provided a comprehensive research of the limits of interference into the human genome. Results: The concept of the human genome, as well as its material and non-material components, have been studied from a biological and legal point of view. The private and legal nature of the human genome as a personal non-property good has been defined. The concept of the individual’s integrity, enshrined in international regulatory legal acts, has been analyzed from the point of view of its coverage of a human being’s genomic integrity. It has been established that a violation of genomic integrity is possible both by the intentional actions of third parties and as a result of genome changes due to the action of natural factors. The concepts and types of the human genome editing have been defined. The potential reasons for banning the editing of human germline cells have been critically analyzed. The legal nature of interference into the human genome from the point of view of eugenical practices has been studied. The author has studied the possibility of classifying the use of vaccines on the mRNA platform as interferences into the human genome. Conclusions: It has been concluded that there is a need to recognize the human genome as a personal non-property good, and, accordingly, as an object of private rights. The author has stated own point of view on the inadmissibility of arbitrary interference into human genomic integrity and the existing types of interference into the human genome.

Fine Mapping Regulatory Variants by Characterizing Native CpG Methylation with Nanopore Long-Read Sequencing.

5-methylcytosine (5mC) is the most common chemical modification occurring on the CpG sites across the human genome. Bisulfite conversion combined with short-read whole genome sequencing can capture and quantify the modification at single nucleotide resolution. However, the PCR amplification process could lead to duplicative methylation patterns and introduce 5mC detection bias. Additionally, the limited read length also restricts co-methylation analysis between distant CpG sites. The bisulfite conversion process presents a significant challenge for detecting variant-specific methylation due to the destruction of allele information in the sequencing reads. To address these issues, we sought to characterize the human methylation profiling with the nanopore long-read sequencing, aiming to demonstrate its potential for long-range co-methylation analysis with native modification call and intact allele information retained. In this regard, we first analyzed the nanopore demo data in the adaptive sampling sequencing run targeting all human CpG islands. We applied the linkage disequilibrium (LD) R2 to calculate the co-methylation in nanopore data, and further identified 27,875, 50,481, 26,542 and 51,189 methylation haplotype blocks (MHB) in COLO829, COLO829BL, HCC1395 and HCC1395BL cell lines, respectively. Interestingly, while we found that majority of the co-methylation were in a short range (≤200bp), a small portion (1~3%) showed long distance (≥1,000bp), suggesting potential remote regulatory mechanisms across the genome. To further characterize the epigenetic changes related to transcription factor binding, we profiled the 5mC percentage changes surrounding various motif sites in JASPAR collection and found that CTCF and KLF5 binding sites showed reduced methylation, while FOXE1 and ZNF354A sites showed increased methylation. To further investigate the allele-specific 5mCG in the prostate genome, we designed a target region covering methylation quantitative trait loci (mQTL) and genome-wide association study (GWAS) risk germline variants and generated long reads with adaptive sampling run in the 22Rv1 cell line. To identify the allele-specific methylation in the 22Rv1 cell line, we performed long-read based phasing and compared the 5mCG signals between the two haplotypes. As a result, we identified 6,390 haplotype-specific methylated regions in the 22Rv1 cell line (p-MWU ≤ 1e-5 and delta ≥ 50%). By examining haplotype-specific methylated regions near the phasing variants, we identified examples of allele-specific methylated regions that showed allelespecific accessibility in the ATAC-seq data. By further integrating the ATAC-seq data of 22Rv1, we found that methylation levels were negatively correlated with chromatin accessibility at the genome-wide scale. Our study has revealed native methylome profiling while preserving haplotype information, offering a novel approach to uncovering the regulatory mechanisms of the human prostate genome.

Before We Forget its Horrors: When Does Human Genome Editing Not Become Eugenics?

Before We Forget its Horrors: When Does Human Genome Editing Not Become Eugenics?

Selective Effect of DNA N6-Methyladenosine Modification on Transcriptional Genetic Variations in East Asian Samples.

Genetic variations and DNA modification are two common dominant factors ubiquitous across the entire human genome and induce human disease, especially through static genetic variations in DNA or RNA that cause human genetic diseases. DNA N6-methyladenosine (6mA) methylation, as a new epigenetic modification mark, has been widely studied for regulatory biological processes in humans. However, the effect of DNA modification on dynamic transcriptional genetic variations from DNA to RNA has rarely been reported. Here, we identified DNA, RNA and transcriptional genetic variations from Illumina short-read sequencing data in East Asian samples (HX1 and AK1) and detected global DNA 6mA modification using single-molecule, real-time sequencing (SMRT) data. We decoded the effects of DNA 6mA modification on transcriptional genetic variations in East Asian samples and the results were extensively verified in the HeLa cell line. DNA 6mA modification had a stabilized distribution in the East Asian samples and the methylated genes were less likely to mutate than the non-methylated genes. For methylated genes, the 6mA density was positively correlated with the number of variations. DNA 6mA modification had a selective effect on transcriptional genetic variations from DNA to RNA, in which the dynamic transcriptional variations of heterozygous (0/1 to 0/1) and homozygous (1/1 to 1/1) were significantly affected by 6mA modification. The effect of DNA methylation on transcriptional genetic variations provides new insights into the influencing factors of DNA to RNA transcriptional regulation in the central doctrine of molecular biology.

Canonical and Non-Canonical Roles of Human DNA Polymerase η.

DNA damage tolerance pathways that allow for the completion of replication following fork arrest are critical in maintaining genome stability during cell division. The main DNA damage tolerance pathways include strand switching, replication fork reversal and translesion synthesis (TLS). The TLS pathway is mediated by specialised DNA polymerases that can accommodate altered DNA structures during DNA synthesis, and are important in allowing replication to proceed after fork arrest, preventing fork collapse that can generate more deleterious double-strand breaks in the genome. TLS may occur directly at the fork, or at gaps remaining behind the fork, in the process of post-replication repair. Inactivating mutations in the human POLH gene encoding the Y-family DNA polymerase Pol η causes the skin cancer-prone genetic disease xeroderma pigmentosum variant (XPV). Pol η also contributes to chemoresistance during cancer treatment by bypassing DNA lesions induced by anti-cancer drugs including cisplatin. We review the current understanding of the canonical role of Pol η in translesion synthesis following replication arrest, as well as a number of emerging non-canonical roles of the protein in other aspects of DNA metabolism.

Cross-species evidence for a developmental origin of adult hypersomnia with loss of synaptic adhesion molecules beat-Ia/CADM2.

Idiopathic hypersomnia (IH) is a poorly-understood sleep disorder characterized by excessive daytime sleepiness despite normal nighttime sleep. Combining human genomics with behavioral and mechanistic studies in fish and flies, we uncover a role for beat-Ia/CADM2 , synaptic adhesion molecules of the immunoglobulin superfamily, in excessive sleepiness. Neuronal knockdown of Drosophila beat-Ia results in sleepy flies and loss of the vertebrate ortholog of beat-Ia , CADM2 , results in sleepy fish. We delineate a developmental function for beat-Ia in synaptic elaboration of neuropeptide F (NPF) neurites projecting to the suboesophageal zone (SEZ) of the fly brain. Brain connectome and experimental evidence demonstrate these NPF outputs synapse onto a subpopulation of SEZ GABAergic neurons to stabilize arousal. NPF is the Drosophila homolog of vertebrate neuropeptide Y (NPY), and an NPY receptor agonist restores sleep to normal levels in zebrafish lacking CADM2 . These findings point towards NPY modulation as a treatment target for human hypersomnia.

The formation and propagation of human Robertsonian chromosomes.

Robertsonian chromosomes are a type of variant chromosome found commonly in nature. Present in one in 800 humans, these chromosomes can underlie infertility, trisomies, and increased cancer incidence. Recognized cytogenetically for more than a century, their origins have remained mysterious. Recent advances in genomics allowed us to assemble three human Robertsonian chromosomes completely. We identify a common breakpoint and epigenetic changes in centromeres that provide insight into the formation and propagation of common Robertsonian translocations. Further investigation of the assembled genomes of chimpanzee and bonobo highlights the structural features of the human genome that uniquely enable the specific crossover event that creates these chromosomes. Resolving the structure and epigenetic features of human Robertsonian chromosomes at a molecular level paves the way to understanding how chromosomal structural variation occurs more generally, and how chromosomes evolve.

Gene expansions contributing to human brain evolution.

Genomic drivers of human-specific neurological traits remain largely undiscovered. Duplicated genes expanded uniquely in the human lineage likely contributed to brain evolution, including the increased complexity of synaptic connections between neurons and the dramatic expansion of the neocortex. Discovering duplicate genes is challenging because the similarity of paralogs makes them prone to sequence-assembly errors. To mitigate this issue, we analyzed a complete telomere-to-telomere human genome sequence (T2T-CHM13) and identified 213 duplicated gene families likely containing human-specific paralogs (>98% identity). Positing that genes important in universal human brain features should exist with at least one copy in all modern humans and exhibit expression in the brain, we narrowed in on 362 paralogs with at least one copy across thousands of ancestrally diverse genomes and present in human brain transcriptomes. Of these, 38 paralogs co-express in gene modules enriched for autism-associated genes and potentially contribute to human language and cognition. We narrowed in on 13 duplicate gene families with human-specific paralogs that are fixed among modern humans and show convincing brain expression patterns. Using long-read DNA sequencing revealed hidden variation across 200 modern humans of diverse ancestries, uncovering signatures of selection not previously identified, including possible balancing selection of CD8B. To understand the roles of duplicated genes in brain development, we generated zebrafish CRISPR "knockout" models of nine orthologs and transiently introduced mRNA-encoding paralogs, effectively "humanizing" the larvae. Morphometric, behavioral, and single-cell RNA-seq screening highlighted, for the first time, a possible role for GPR89B in dosage-mediated brain expansion and FRMPD2B function in altered synaptic signaling, both hallmark features of the human brain. Our holistic approach provides important insights into human brain evolution as well as a resource to the community for studying additional gene expansion drivers of human brain evolution.

Severity Ranking of Missense and Frameshift Genetic Variants in SCD1 by In Silico and In Vitro Functional Analysis.

A considerable proportion of the symptoms associated with excessive dietary intake can be attributed to systemic imbalances in lipid metabolism. The prominent toxicity of saturated fatty acids has been repeatedly demonstrated and sheds light on the protective role of stearoyl-CoA desaturase-1 (SCD1), the key enzyme for fatty acid desaturation. SCD1 protein expression is regulated at the levels of transcription, translation, and degradation. However, the modulating effect of the variability of the human genome must also be taken into account. Therefore, we aimed to ascertain whether natural missense or frameshift mutations in SCD1 (p.H125P, p.M224L, p.A333T, p.R253AfsTer7) could influence the expression, degradation, or function of the enzyme. In silico and in vitro experiments were conducted to comprehensively evaluate the consequences associated with each genetic variation, with the objective of using the results to propose a risk or severity ranking of SCD1 variants. As anticipated, the p.R253AfsTer7 variant was identified as the most deleterious in structural, functional, and quantitative terms. The p.H125P variant also reduced the desaturation capacity of the enzyme in accordance with the predicted structural alterations and augmented degradation resulting from folding complications. This was aggravated by increased mRNA instability and accompanied by mild endoplasmic reticulum stress induction. The p.A333T protein exhibited an intermediate phenotype, whereas p.M224L showed no deleterious effects and even increased the amount of SCD1. In conclusion, the large-scale identification of genetic variations needs to be supplemented with comprehensive functional characterization of these variations to facilitate adequate personalized prevention and treatment of lipid metabolism-related conditions.

Peculiar k-mer Spectra Are Correlated with 3D Contact Frequencies and Breakpoint Regions in the Human Genome.

It is widely accepted that the 3D chromatin organization in human cell nuclei is not random and recent investigations point towards an interactive relation of epigenetic functioning and chromatin (re-)organization. Although chromatin organization seems to be the result of self-organization of the entirety of all molecules available in the cell nucleus, a general question remains open as to what extent chromatin organization might additionally be predetermined by the DNA sequence and, if so, if there are characteristic differences that distinguish typical regions involved in dysfunction-related aberrations from normal ones, since typical DNA breakpoint regions involved in disease-related chromosome aberrations are not randomly distributed along the DNA sequence. Highly conserved k-mer patterns in intronic and intergenic regions have been reported in eukaryotic genomes. In this article, we search and analyze regions deviating from average spectra (ReDFAS) of k-mer word frequencies in the human genome. This includes all assembled regions, e.g., telomeric, centromeric, genic as well as intergenic regions. A positive correlation between k-mer spectra and 3D contact frequencies, obtained exemplarily from given Hi-C datasets, has been found indicating a relation of ReDFAS to chromatin organization and interactions. We also searched and found correlations of known functional annotations, e.g., genes correlating with ReDFAS. Selected regions known to contain typical breakpoints on chromosomes 9 and 5 that are involved in cancer-related chromosomal aberrations appear to be enriched in ReDFAS. Since transposable elements like ALUs are often assigned as major players in 3D genome organization, we also studied their impact on our examples but could not find a correlation between ALU regions and breakpoints comparable to ReDFAS. Our findings might show that ReDFAS are associated with instable regions of the genome and regions with many chromatin contacts which is in line with current research indicating that chromatin loop anchor points lead to genomic instability.

Complex genetic variation in nearly complete human genomes.

Diverse sets of complete human genomes are required to construct a pangenome reference and to understand the extent of complex structural variation. Here, we sequence 65 diverse human genomes and build 130 haplotype-resolved assemblies (130 Mbp median continuity), closing 92% of all previous assembly gaps1,2 and reaching telomere-to-telomere (T2T) status for 39% of the chromosomes. We highlight complete sequence continuity of complex loci, including the major histocompatibility complex (MHC), SMN1/SMN2, NBPF8, and AMY1/AMY2, and fully resolve 1,852 complex structural variants (SVs). In addition, we completely assemble and validate 1,246 human centromeres. We find up to 30-fold variation in α-satellite high-order repeat (HOR) array length and characterize the pattern of mobile element insertions into α-satellite HOR arrays. While most centromeres predict a single site of kinetochore attachment, epigenetic analysis suggests the presence of two hypomethylated regions for 7% of centromeres. Combining our data with the draft pangenome reference1 significantly enhances genotyping accuracy from short-read data, enabling whole-genome inference3 to a median quality value (QV) of 45. Using this approach, 26,115 SVs per sample are detected, substantially increasing the number of SVs now amenable to downstream disease association studies.

P53motifDB: integration of genomic information and tumor suppressor p53 binding motifs.

The tumor suppressor gene TP53 encodes the DNA binding transcription factor p53 and is one of the most commonly mutated genes in human cancer. Tumor suppressor activity requires binding of p53 to its DNA response elements and subsequent transcriptional activation of a diverse set of target genes. Despite decades of close study, the logic underlying p53 interactions with its numerous potential genomic binding sites and target genes is not yet fully understood. Here, we present a database of DNA and chromatin-based information focused on putative p53 binding sites in the human genome to allow users to generate and test new hypotheses related to p53 activity in the genome. Users can query genomic locations based on experimentally observed p53 binding, regulatory element activity, genetic variation, evolutionary conservation, chromatin modification state, and chromatin structure. We present multiple use cases demonstrating the utility of this database for generating novel biological hypotheses, such as chromatin-based determinants of p53 binding and potential cell type-specific p53 activity. All database information is also available as a precompiled sqlite database for use in local analysis or as a Shiny web application.

AGAP duplicons associate with structural diversity at Chromosome 10q11.22.

The 10q11.22 chromosomal region is a duplication-rich interval of the human genome and one of the last to be fully assembled. It carries copy-number variable genes associated with intellectual disability, bipolar disorder, and obesity. In this study, we characterized the structural diversity at this locus by analyzing 64 haploid assemblies produced by the Human Pangenome Reference Consortium. We identified eleven alternative haplotypes that differ in the copy number and/or orientation of large genomic segments, ranging from hundreds of kilobase pairs (kbp) to over one megabase pair (Mbp). We uncovered a 2.4 Mbp size difference between the shortest and longest haplotypes. Breakpoint analysis revealed that genomic instability results from nonallelic homologous recombination between segmental duplication (SD) pairs with varying similarity (94.4-99.6%). Nonetheless, these pairs generally recombine at positions where their identity is higher (>99.6%). Recurrent inversions occur with varying breakpoints within the same inverted SD pair. Inversion polymorphisms shuffle the entire SD arrangement, creating new predispositions to copy-number variations. The SD architecture is associated with a catarrhine-specific subgroup of the AGAP gene family, which likely triggered the accumulation of SDs at this locus over the past 25 million years of human evolution. Our results reveal extensive structural diversity and genomic instability at the 10q11.22 locus and expand the general understanding of the mutational mechanisms behind SD-mediated rearrangements.

The influence of G-tract and loop length on the topological variability of putative five and six G-quartet DNA structures in the human genome

Local variation of DNA structure and its dynamic nature play an essential role in the regulation of important biological processes. One of the most prominent noncanonical structures are G-quadruplexes, which form in vivo within guanine-rich regions and have been demonstrated to be involved in the regulation of transcription, translation and telomere maintenance. We provide an analysis of G-quadruplex formation in sequences with five and six guanine residues long G-tracts, which have emerged from the investigation of the gapless human genome and are associated with genes related to cancer and neurodegenerative diseases. We systematically explored the effect of G-tract and loop elongations by means of NMR and CD spectroscopy and polyacrylamide electrophoresis. Despite both types of elongation leading up to structural polymorphism, we successfully determined the topologies of four out of eight examined sequences, one of which contributes to a very scarce selection of currently known intramolecular four G-quartet structures in potassium solutions. We demonstrate that examined sequences are incompatible with five or six G-quartet structures with propeller loops, although the compatibility with other loop types cannot be factored out. Lastly, we propose a novel approach towards specific G-quadruplex targeting that could be implemented in structures with more than four G-quartets.

Ethical, Legal, and Social Implications of Gene-Environment Interaction Research.

Many complex disorders are impacted by the interplay of genetic and environmental factors. In gene-environment interactions (GxE), an individual's genetic and epigenetic makeup impacts the response to environmental exposures. Understanding GxE can impact health at the individual, community, and population levels. The rapid expansion of GxE research in biomedical studies for complex diseases raises many unique ethical, legal, and social implications (ELSIs) that have not been extensively explored and addressed. This review article builds on discussions originating from a workshop held by the National Institute of Environmental Health Sciences (NIEHS) and the National Human Genome Research Institute (NHGRI) in January 2022, entitled: "Ethical, Legal, and Social Implications of Gene-Environment Interaction Research." We expand upon multiple key themes to inform broad recommendations and general guidance for addressing some of the most unique and challenging ELSI in GxE research. Key takeaways include strategies and approaches for establishing sustainable community partnerships, incorporating social determinants of health and environmental justice considerations into GxE research, effectively communicating and translating GxE findings, and addressing privacy and discrimination concerns in all GxE research going forward. Additional guidelines, resources, approaches, training, and capacity building are required to further support innovative GxE research and multidisciplinary GxE research teams.

Pangenome-Informed Language Models for Privacy-Preserving Synthetic Genome Sequence Generation.

The public availability of genome datasets, such as The Human Genome Project (HGP), The 1000 Genomes Project, The Cancer Genome Atlas, and the International HapMap Project, has significantly advanced scientific research and medical understanding. Here our goal is to share such genomic information for downstream analysis while protecting the privacy of individuals through Differential Privacy (DP). We introduce synthetic DNA data generation based on pangenomes in combination with Pretrained-Language Models (PTLMs). We introduce two novel tokenization schemes based on pangenome graphs to enhance the modeling of DNA. We evaluated these tokenization methods, and compared them with classical single nucleotide and k -mer tokenizations. We find k -mer tokenization schemes, indicating that our tokenization schemes boost the model's performance consistency with long effective context length (covering longer sequences with the same number of tokens). Additionally, we propose a method to utilize the pangenome graph and make it comply with DP privacy standards. We assess the performance of DP training on the quality of generated sequences with discussion of the trade-offs between privacy and model accuracy. The source code for our work will be published under a free and open source license soon.

SpEpistasis: A sparse approach for three-way epistasis detection

Epistasis detection is a fundamental application in the areas of bioinformatics and biomedicine, providing important insights regarding the relationship between the human genome and the occurrence of certain diseases. Exhaustive epistasis detection approaches are employed to achieve an accurate and deterministic solution, at the cost of high computational complexity, especially when targeting high-order epistasis. While recent works employ vectorization and cache-blocking techniques to alleviate this burden, these solutions are now limited by the maximum performance of the functional units of computing systems. Thus, to further improve the performance of epistasis detection it is necessary to reduce its number of memory transfers and computations. To tackle this issue, this work proposes SpEpistasis, which performs three-way epistasis detection by relying on sparse features, which by only storing the non-zero elements of the dataset, allows for reducing the number of operations needed for epistasis detection. To achieve this goal, a new hybrid format to represent the input dataset is proposed, which stores a subset of the data in the compressed sparse row format. Moreover, new sparse-aware algorithmic approaches are also proposed in order to leverage both the hybrid format and the vector capabilities of current CPUs from Intel, AMD, and ARM. The experimental results show that SpEpistasis provides a speedup up to 3.7× and average speedups of around 1.8× and 1.33× when compared with other state-of-the-art works.

The repertoire of G-protein-coupled receptor variations in the Japanese population 54KJPN.

G-protein-coupled receptors (GPCRs) are the largest superfamily in the human genome and the major targets for the market drugs. Recent massive genomics studies revealed numerous natural variations in the general population. 54KJPN is the most extensive Japanese population genomics study, curating the whole genome sequences from about 54,000 individuals. Here, by analyzing 390 non-olfactory GPCR genes in the 54KJPN dataset, we annotated 25,443 missense single-nucleotide variations. Among them, we found 120 major variations that appear with an allele frequency greater than 0.5, including variations that occurred on posttranslational modification sites. Structural alignment of GPCRs using the generic numbering system in the GPCRdb reveals enrichment of alterations in the conserved arginine residue within the DRY motif, which contributes to downstream G-protein signaling. A comparison with the worldwide 1000 Genomes Project (1KGP) dataset found 23 variations that were present exclusively in the 54KJPN dataset. This study will be the basis for future pharmacogenomics studies for the Japanese population.

Semi-supervised learning with pseudo-labeling compares favorably with large language models for regulatory sequence prediction.

Predicting molecular processes using deep learning is a promising approach to provide biological insights for non-coding single nucleotide polymorphisms identified in genome-wide association studies. However, most deep learning methods rely on supervised learning, which requires DNA sequences associated with functional data, and whose amount is severely limited by the finite size of the human genome. Conversely, the amount of mammalian DNA sequences is growing exponentially due to ongoing large-scale sequencing projects, but in most cases without functional data. To alleviate the limitations of supervised learning, we propose a novel semi-supervised learning (SSL) based on pseudo-labeling, which allows to exploit unlabeled DNA sequences from numerous genomes during model pre-training. We further improved it incorporating principles from the Noisy Student algorithm to predict the confidence in pseudo-labeled data used for pre-training, which showed improvements for transcription factor with very few binding (very small training data). The approach is very flexible and can be used to train any neural architecture including state-of-the-art models, and shows in most cases strong predictive performance improvements compared to standard supervised learning. Moreover, small models trained by SSL showed similar or better performance than large language model DNABERT2.

Bioinformatics in Russia: history and present-day landscape.

Bioinformatics has become an interdisciplinary subject due to its universal role in molecular biology research. The current status of Russia's bioinformatics research in Russia is not known. Here, we review the history of bioinformatics in Russia, present the current landscape, and highlight future directions and challenges. Bioinformatics research in Russia is driven by four major industries: information technology, pharmaceuticals, biotechnology, and agriculture. Over the past three decades, despite a delayed start, the field has gained momentum, especially in protein and nucleic acid research. Dedicated and shared centers for genomics, proteomics, and bioinformatics are active in different regions of Russia. Present-day bioinformatics in Russia is characterized by research issues related to genetics, metagenomics, OMICs, medical informatics, computational biology, environmental informatics, and structural bioinformatics. Notable developments are in the fields of software (tools, algorithms, and pipelines), use of high computation power (e.g. by the Siberian Supercomputer Center), and large-scale sequencing projects (the sequencing of 100 000 human genomes). Government funding is increasing, policies are being changed, and a National Genomic Information Database is being established. An increased focus on eukaryotic genome sequencing, the development of a common place for developers and researchers to share tools and data, and the use of biological modeling, machine learning, and biostatistics are key areas for future focus. Universities and research institutes have started to implement bioinformatics modules. A critical mass of bioinformaticians is essential to catch up with the global pace in the discipline.