Alignment Program Research Articles

High scoring segment selection for pairwise whole genome sequence alignment with the maximum scoring subsequence and GPUs

Whole genome alignment programs use string matching with hash tables to identify high scoring fragments between a query and target sequence around which a full alignment is then built. A recent study comparing alignment programs showed that while evolutionary similar genomes were easy to align, divergent genomes still posed a challenge to existing methods. To fill this gap we explore the use of the maximum scoring subsequence to identify high scoring fragments. We split the query genome into several fragments and align them to the target with a previously published parallel algorithm for short read alignment. We then pass such high scoring fragments on to the LASTZ program to obtain a more complete alignment. On simulated data we obtain an average of at least 20% higher accuracy than the alignment given by LASTZ at the expense of few hours of additional runtime. Our source code is freely available at http://web.njit.edu/usman/MSGA

Genetic characterization and phylogenetic study of Indonesian indigenous catfish based on mitochondrial cytochrome B gene.

Aims:This study aimed to determine the genetic characterization and phylogenetic structure of Indonesian indigenous catfish using cytochrome B (Cyt B) sequences.Materials and Methods:The genomes of 26 catfishes caught from nine rivers from nine different geographical locations around Indonesia were analyzed. The tissue isolation method was used to isolate the total genome of the fishes. Furthermore, polymerase chain reaction was done to amplify the mtDNA Cyt B using the CytBF and CytBR primers. Following sequencing, the analysis of genetic variation and the phylogenetic relationship was performed using MEGA version X software.Results:Cyt B gene sequencing attained a total of 1139 nucleotides encrypting 379 amino acids for all samples. The ClustalW alignment program using MEGA X software revealed 395 substituted nucleotides, which then translated into 63 amino acid variation sites among all 26 samples. No amino acids in catfish BB were different compared to catfish PM, MP, and KR2,3. Catfish MS had one modified amino acid; KR1 and KS had two different amino acids; BF had 38 different amino acids; EM had 31 different amino acids; and BSBJ had 26 different amino acids compared to catfish BB. The most significant alteration of amino acids was between catfish EM and BF (49 amino acids).Conclusion:Indonesian catfish were divided into five clades based on the Cyt B gene. Samples KR and MP (Sumatra); MS and BB (Kalimantan); and PM (Java) were clustered with Hemibagrus nemurus and Hemibagrus wyckioides (Bagridae family). Samples from Kalimantan (KS) and one sample of KR (KR1) from Sumatra were clustered with Sperata seenghala and Hemibagrus spilopterus (Bagridae family). Samples from Java (BSBJ) were clustered with Pseudolais pleurotaenia (Pangasiidae family). Samples EM (Java) were together with Mystus cavasius (Bagridae family). Samples from West Papua were clustered with Potamosilurus latirostris (Ariidae family).

A customized program for the identification of conserved protein sequence motifs.

We searched for viral protein sequences that could be important for tissue tropism. To achieve this goal, human pathogenic viruses were classified according to the tissue they infect (e.g., pulmonary), irrespective of whether they were enveloped or non-enveloped RNA or DNA viruses. Next, we developed an amino acid sequence alignment program and identified the conserved amino acid motif, VAIVLGG, in alphaviruses. The VAIVLGG sequence is located on the structural capsid protein of the chikungunya virus, a mosquito-borne arthrogenic member of the alphaviruses. Capsid protein translocation onto the host cell membrane is a required step for virion budding. Our identified VAIVLGG consensus sequence might potentially be used for developing a pan-vaccine effective against alphaviruses.

DNA barcoding of different Triticum species

BackgroundThe genus Triticum L. includes diploid, tetraploid, and hexaploid species. DNA barcoding is a new method to identify plant taxa by using short sequences of DNA and within a short time. In this investigation, we determined a phylogenetic analysis of 20 different Triticum species by partial chloroplast Maturase encoding gene (matK).Materials and methodsTwenty accessions of different Triticum species diploid, tetraploid, and hexaploid were obtained from different countries. Genomic DNA was isolated from young leaves of studied samples and then used as a template for PCR reaction. PCR products were checked by electrophoresis, purified, sequenced, and submitted in the GenBank nucleotide sequence database, the nucleotide sequence was translated into an amino acid sequence. The nucleotide and amino acid sequences were aligned with Clustal W multiple sequence alignment programs to obtain the phylogenetic tree depending on two statistical data analysis such as bootstrapping and pairwise distance from both nucleotide and amino acid sequences.ResultsThe phylogenetic tree obtained from both nucleotide and amino acid sequences divided the 20 Triticum species into two groups, A and B. Group A represented the diploid Triticum species. Group B was divided into two subgroup, I and II. Subgroup I represented the hexaploid Triticum species and subgroup II represented the tetraploid species.ConclusionThe matK gene sequence has a critical role in discriminating the closely related Triticum species. So these sequences could be used as a DNA barcode for detecting the evolutionary history of Triticum species.

AGONOTES: A Robot Annotator for Argonaute Proteins.

The argonaute protein (Ago) exists in almost all organisms. In eukaryotes, it functions as a regulatory system for gene expression. In prokaryotes, it is a type of defense system against foreign invasive genomes. The Ago system has been engineered for gene silencing and genome editing and plays an important role in biological studies. With an increasing number of genomes and proteomes of various microbes becoming available, computational tools for identifying and annotating argonaute proteins are urgently needed. We introduce AGONOTES (Argonaute Notes). It is a web service especially designed for identifying and annotating Ago. AGONOTES uses the BLASTP similarity search algorithm to categorize all submitted proteins into three groups: prokaryotic argonaute protein (pAgo), eukaryotic argonaute protein (eAgo), and non-argonaute protein (non-Ago). Argonaute proteins can then be aligned to the corresponding standard set of Ago sequences using the multiple sequence alignment program MUSCLE. All functional domains of Ago can further be curated from the alignment results and visualized easily through Bio::Graphic modules in the BioPerl bundle. Compared with existing tools such as CD-Search and available databases such as UniProt and AGONOTES showed a much better performance on domain annotations, which is fundamental in studying the new Ago. AGONOTES can be freely accessed at http://i.uestc.edu.cn/agonotes/. AGONOTES is a friendly tool for annotating Ago domains from a proteome or a series of protein sequences.

Kalign 3: multiple sequence alignment of large data sets.

MotivationKalign is an efficient multiple sequence alignment (MSA) program capable of aligning thousands of protein or nucleotide sequences. However, current alignment problems involving large numbers of sequences are exceeding Kalign’s original design specifications. Here we present a completely re-written and updated version to meet current and future alignment challenges.ResultsKalign now uses a SIMD (single instruction, multiple data) accelerated version of the bit-parallel Gene Myers algorithm to estimate pairwise distances, adopts a sequence embedding strategy and the bi-secting K-means algorithm to rapidly construct guide trees for thousands of sequences. The new version maintains high alignment accuracy on both protein and nucleotide alignments and scales better than other MSA tools.Availability and implementationThe source code of Kalign and code to reproduce the results are found here: https://github.com/timolassmann/kalign.

Impact of Student Perceptions of the Educational Program on Burnout in Medical School.

Burnout is considered to be at the opposite end of the continuum from engagement. People who experience burnout first go through various intermediate patterns that lead to burnout, which in medical students is associated with reduced empathy, intention to leave school, and suicidal ideation. Thus, understanding how to mitigate burnout is of primary importance. In this study, we investigate if students' positive perceptions of the educational program's alignment with adult education principles decreased symptoms suggestive of typical patterns of intermediate burnout. We conducted a cross-sectional survey study of all currently enrolled Duke-NUS Medical School students in Singapore (n = 238). An electronic questionnaire contained demographic questions and additional measures for factors known to be associated with burnout, including depression, anxiety, social support, and workload. In addition, we measured students' perceptions of how well the educational program aligned with adult learning principles by using a modified version of the Andragogical Practices Inventory (API) to suit medical education. An intermediate pattern of burnout was measured using the Maslach Burnout Inventory (MBI). Using logistic regression, we then assessed the unique association between the presence of an intermediate pattern of burnout with students' perceptions of the educational program's alignment with adult learning principles. The survey response rate was 52%. Overall, 76% (95% CI 67-84%) displayed symptoms suggestive of an intermediate pattern of burnout. Perceptions of the educational program's alignment with adult learning principles were found to be inversely related to the pattern of burnout after controlling for depression, anxiety, and subjective workload. Though adult learning theory is the subject of rich debate, the results of this study suggest that promoting educational activities that are aligned with adult learning principles may help to ultimately reduce the risk of burnout in medical school students.

Numerical investigation of after stern tube bearing during ship turning maneuver

Large propeller lateral loads during ship turning maneuver may cause serious damage on after stern tube bearing. Failure of after stern tube bearing frequently occurs, especially when environmentally acceptable lubricants are used in the ship’s stern tube. Therefore, a new design rule for after stern bearing is urgently needed. This paper presents a numerical investigation on the oil film performance of the after stern tube bearing of a super handy-max bulk carrier in turning maneuver. Computational fluid dynamics is adopted to estimate the propeller lateral forces and moments, which are introduced into the shafting alignment calculation. In shafting alignment analysis, the after stern tube bearing is divided into several bearing segments, and the midpoint of journal segments is used to characterize the deflection of the journal centerline. The accurate deflection of the journal center of the after stern tube bearing is obtained through the iteration of the shafting alignment program and Reynolds equation. Moreover, the distribution of oil film pressure and the minimum oil film thickness are recorded. Finally, the criterion for oil film is discussed.

Genome-wide nucleotide variation distinguishes Aspergillus flavus from Aspergillus oryzae and helps to reveal origins of atoxigenic A. flavus biocontrol strains.

To use genome-wide single nucleotide polymorphisms (total SNPs) to develop a molecular method for distinguishing Aspergillus flavus and Aspergillus oryzae. Thirteen A. flavus and eleven A. oryzae genome sequences were obtained from the National Center for Biotechnology Information. These sequences were analysed by Mauve, a multiple-genome alignment program, to extract total SNPs between isolates of A. flavus, A. oryzae, or the two species. Averages of total SNPs of A. flavus isolates belonging to the same sclerotial morphotype (L-type=178952±14033; S-type=133188±16430) and A. oryzae isolates (152336±49124) were consistently lower than those between the morphotypes and between the two species. Averages of total SNPs for L-type vs S-type (300116±1562) and S-type A. flavus vs A. oryzae (301797±4123) were similar but were 36% greater than that of L-type A. flavus vs A. oryzae (226240±10779). Based on the devised criterion, ATCC 12892, Aspergillus oryzae (Ahlburg) Cohn, which had an averaged total SNPs 10-fold greater than that of other A. oryzae isolates, was determined to be close to Aspergillus parasiticus. Atoxigenic A. flavus field isolates, WRRL1519 and NRRL35739, were shown to more closely resemble A. oryzae than toxigenic L-type A. flavus. Biocontrol strains AF36 and K49 were genetically close to toxigenic L-type A. flavus. NRRL21882, the active agent of the commercialized biocontrol product Afla-Guard® GR, was genetically distant from all other A. flavus isolates. The close genetic relatedness between A. flavus and A. oryzae was confirmed and the evolutionary origins of atoxigenic A. flavus biocontrol strains were revealed. The study provides a greater understanding of genome similarity and dissimilarity between A. flavus and A. oryzae. The method can be an auxiliary technique for identifying A. flavus, A. oryzae.

8주간의 스트레칭과 코어 운동 프로그램이 청소년의 자세교정에 미치는 효과에 관한 비교분석

This study aims to provide exercise program for correct body alignment of the youth in the growth period, to identify the factors that can be improved through correct posture and to improve the quality of the youth in growth period. For this purpose, this study conducted a group exercise for 60 minutes 2 times a week and a personal home training program one time a week on the experimental group 1(7 persons) applied with stretching exercise and experimental group 2(10 persons) applied with core props exercise program for 8 weeks. By examining and analyzing changes in 3 dimensional posture measurement variables before and after application of program, that is, arrangement status of the spine, imbalance of body central axis, rotation of spine and torso torsion using formetric 4D, this study obtained the results as follows. First, significant difference between group was found in Scoliosis and Kyphosis among Vertebra factors(p<0.5). Second, significant difference between group was found in pelvic rotation and pelvic torsion among pelvic factors(p<0.5). No significant difference was found in the factors of torso twist, rotation of pelvis and imbalance of central axis.

Impact of alignment algorithm on the estimation of pairwise genetic similarity of porcine reproductive and respiratory syndrome virus (PRRSV)

BackgroundPorcine reproductive and respiratory syndrome (PRRS) is a major threat to the swine industry. It is caused by the PRRS virus (PRRSV). Determination and comparison of the nucleotide sequences of PRRSV strains provides useful information in support of control initiatives or epidemiological studies on transmission patterns. The alignment of sequences is the first step in analyzing sequence data, with multiple algorithms being available, but little is known on the impact of this methodological choice. Here, a study was conducted to evaluate the impact of different alignment algorithms on the resulting aligned sequence dataset and on practical issues when applied to a large field database of PRRSV open reading frame (ORF) 5 sequences collected in Quebec, Canada, from 2010 to 2014. Five multiple sequence alignment programs were compared: Clustal W, Clustal Omega, Muscle, T-Coffee and MAFFT.ResultsThe resulting alignments showed very similar results in terms of average pairwise genetic similarity, proportion of pairwise comparisons having ≥97.5% genetic similarity and sum of pairs (SP) score, except for T-Coffee where increased length of aligned datasets as well as limitation to handle large datasets were observed.ConclusionsBased on efficiency at minimizing the number of gaps in different dataset sizes with default open gap values as well as the capability to handle a large number of sequences in a timely manner, the use of Clustal Omega might be recommended for the management of PRRSV extensive database for both research and surveillance purposes.

RNA-align: quick and accurate alignment of RNA 3D structures based on size-independent TM-scoreRNA.

Comparison of RNA 3D structures can be used to infer functional relationship of RNA molecules. Most of the current RNA structure alignment programs are built on size-dependent scales, which complicate the interpretation of structure and functional relations. Meanwhile, the low speed prevents the programs from being applied to large-scale RNA structural database search. We developed an open-source algorithm, RNA-align, for RNA 3D structure alignment which has the structure similarity scaled by a size-independent and statistically interpretable scoring metric. Large-scale benchmark tests show that RNA-align significantly outperforms other state-of-the-art programs in both alignment accuracy and running speed. The major advantage of RNA-align lies at the quick convergence of the heuristic alignment iterations and the coarse-grained secondary structure assignment, both of which are crucial to the speed and accuracy of RNA structure alignments. https://zhanglab.ccmb.med.umich.edu/RNA-align/. Supplementary data are available at Bioinformatics online.

Using a Theoretical Framework as Infrastructure to Strengthen and Align Program Learning Outcomes and Assessments of an Online Leadership Program

Despite growth in online programs in general, and leadership programs in specific, uniform underlying infrastructure or theory models for the basis of leadership programs is lacking (Jones 2005). This paper journals the process undergone by a university faculty as they redesign courses of an online BA in Organizational Leadership. Seemiller’s (2014) Leadership Competencies provided the theoretical framework for each of the leadership courses. The process of selecting and integrating these competencies is explained: the value judgements made to connect the competencies with the design of courses, integration of similar or corollary competencies, and the philosophical reasons for these decisions are discussed

Protein multiple alignments: sequence-based versus structure-based programs.

Multiple sequence alignment programs have proved to be very useful and have already been evaluated in the literature yet not alignment programs based on structure or both sequence and structure. In the present article we wish to evaluate the added value provided through considering structures. We compared the multiple alignments resulting from 25 programs either based on sequence, structure or both, to reference alignments deposited in five databases (BALIBASE 2 and 3, HOMSTRAD, OXBENCH and SISYPHUS). On the whole, the structure-based methods compute more reliable alignments than the sequence-based ones, and even than the sequence+structure-based programs whatever the databases. Two programs lead, MAMMOTH and MATRAS, nevertheless the performances of MUSTANG, MATT, 3DCOMB, TCOFFEE+TM_ALIGN and TCOFFEE+SAP are better for some alignments. The advantage of structure-based methods increases at low levels of sequence identity, or for residues in regular secondary structures or buried ones. Concerning gap management, sequence-based programs set less gaps than structure-based programs. Concerning the databases, the alignments of the manually built databases are more challenging for the programs. All data and results presented in this study are available at: http://wwwabi.snv.jussieu.fr/people/mathilde/download/AliMulComp/. Supplementary data are available at Bioinformatics online.

A comprehensive evaluation of spliced alignment programs of RNA-Seq data

A comprehensive evaluation of spliced alignment programs of RNA-Seq data

Time Efficient Segmented Technique for Dynamic Programming Based Algorithms with FPGA Implementation

Although dynamic programming (DP) is an optimization approach used to solve a complex problem fast, the time required to solve it is still not efficient and grows polynomially with the size of the input. In this contribution, we improve the computation time of the dynamic programming based algorithms by proposing a novel technique, which is called “SDP: Segmented Dynamic programming”. SDP finds the best way of splitting the compared sequences into segments and then applies the dynamic programming algorithm to each segment individually. This will reduce the computation time dramatically. SDP may be applied to any dynamic programming based algorithm to improve its computation time. As case studies, we apply the SDP technique on two different dynamic programming based algorithms; “Needleman–Wunsch (NW)”, the widely used program for optimal sequence alignment, and the LCS algorithm, which finds the “Longest Common Subsequence” between two input strings. The results show that applying the SDP technique in conjunction with the DP based algorithms improves the computation time by up to 80% in comparison to the sole DP algorithms, but with small or ignorable degradation in comparing results. This degradation is controllable and it is based on the number of split segments as an input parameter. However, we compare our results with the well-known heuristic FASTA sequence alignment algorithm, “GGSEARCH”. We show that our results are much closer to the optimal results than the “GGSEARCH” algorithm. The results are valid independent from the sequences length and their level of similarity. To show the functionality of our technique on the hardware and to verify the results, we implement it on the Xilinx Zynq-7000 FPGA.

Calling known variants and identifying new variants while rapidly aligning sequence data

Whole-genome sequencing studies can identify causative mutations for subsequent use in genomic evaluations. Speed and accuracy of sequence alignment can be improved by accounting for known variant locations during alignment instead of calling the variants after alignment as in previous programs. The new programs Findmap and Findvar were compared with alignment using Burrows-Wheeler alignment (BWA) or SNAP and variant identification using Genome Analysis ToolKit (GATK) or SAMtools. Findmap stores the reference map and any known variant locations while aligning reads and counting reference and alternate alleles for each DNA source. Findmap also outputs potential new single nucleotide variant, insertion, and deletion alleles. Findvar separates likely true variants from read errors and outputs genotype probabilities. Strategies were tested using cattle, human, and a completely random reference map and simulated or actual data. Most tests simulated 10 bulls, each with 10× simulated sequence reads containing 39 million variants from the 1000 Bull Genomes Project. With 10 processors, clock times for processing 100× data were 105 h for BWA, 25 h for GATK, and 11 h for SAMtools but only about 4 h for SNAP, 3 h for Findmap, and 1 h for Findvar. Alignment programs required about the same total memory; BWA used 46 GB (4.6 GB/processor), whereas >10 processors can share the same memory in SNAP and Findmap, which used 40 and 46 GB, respectively. Findmap correctly mapped 92.9% of reads (compared with 92.6% from SNAP and 90.5% from BWA) and had high accuracy of calling alleles for known variants. For new variants, Findvar found 99.8% of single nucleotide variants, 79% of insertions, and 67% of deletions; GATK found 99.4, 95, and 90%, respectively; and SAMtools found 99.8, 12, and 16%, respectively. False positives (as percentages of true variants) were 11% of single nucleotide variants, 0.4% of insertions, and 0.3% of deletions from Findvar; 12, 8.4, and 2.9%, respectively, from GATK; and 37, 1.3, and 0.4%, respectively, from SAMtools. Advantages of Findmap and Findvar are fast processing, precise alignment, more useful data summaries, more compact output, and fewer steps. Calling known variants during alignment allows more efficient and accurate sequence-based genotyping.

Genetic Characterization of Argas persicus From Iran by Sequencing of Mitochondrial Cytochrome Oxidase I (COX1) and 16s rRNA Genes

Background: Argas persicus has a great importance for health and veterinary, it can transmit many infectious agents such as Borrelia anserina (avian spirochetosis) and Aegyptianella pullorum. Distinguishing Argasidae due to close morphological relationship is difficult. OBJECTIVES: In the present study, we performed molecular analyses based on PCR and sequencing of Amplicon derived from 16S rRNA and COX1 genes of A. persicus specimens in several provinces of Iran. Methods: Out of seventy Argas persicus collected and confirmed morphologically, eight ticks were chosen from five provinces of Iran for gene analysis. Their DNA were extracted and amplificated using primers derived from 16 S ribosomal RNA and COX1 genes using PCR. Then the amplicons were sequenced and analyzed by Chromas software and sequence alignment program (Clustal W). Phylogenetic analysis was also conducted using MEGA ver. 6.06 with a maximum-likelihood method. RESULTS: Sequencing results indicated that all eight samples belonged to A. persicus species. Their nucleotide sequencing revealed that the interspecific sequence differences of both genes (16S rRNA genes and COX1) between our isolates were very infrequent. All isolates from different provinces were conserved across regions except for one isolate that exhibited a difference of only 1 nucleotide. Within Phylogenetic tree, A. persicus formed a clade with A. persicus from other regions of the world (South Arica, Italy, China, and South Australia). CONCLUSIONS: Our findings suggested a very close phylogenetic relationship between A. persicus specimens obtained from different regions of Iran. Keywords:

BCL::MolAlign: Three-Dimensional Small Molecule Alignment for Pharmacophore Mapping.

Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular alignment program. BCL::MolAlign accommodates ligand flexibility through a combination of pregenerated conformers and on-the-fly bond rotation. BCL::MolAlign converges on alignment poses by sampling the relative orientations of mutually matching atom pairs between molecules through Monte Carlo Metropolis sampling. Across six diverse ligand data sets, BCL::MolAlign flexible alignment outperforms MOE, ROCS, and FLEXS in recovering native ligand binding poses. Moreover, the BCL::MolAlign alignment score is more predictive of ligand activity than maximum common substructure similarity across 10 data sets. Finally, on a recently published benchmark set of 20 high quality congeneric ligand-protein complexes, BCL::MolAlign is able to recover a larger fraction of native binding poses than maximum common substructure-based alignment and RosettaLigand. BCL::MolAlign can be obtained as part of the Biology and Chemistry Library (BCL) software package freely with an academic license or can be accessed via Web server at http://meilerlab.org/index.php/servers/molalign .

SA37 - NEUROINFLAMMATORY GENE EXPRESSION IN HIPPOCAMPUS IN MAJOR DEPRESSIVE DISORDER

Background Major Depressive Disorder (MDD) is a common psychiatric disease for which available medications are often not effective. Full remission from depression is achieved by less than 50 percent of patients using medications that mainly target serotonin or norepinephrine systems (Berton and Nestler, 2006; Rush et al., 2006). The economic burden of depression in the U.S., along with comorbid conditions, is estimated at over $170B and depressive disorders are the leading contributors to global burden of disease (Greenberg et al., 2015; Whiteford et al., 2013). The high prevalence of MDD and modest response to existing therapies compels efforts to better understand and treat the disorder. One promising avenue of research suggests that decreases in hippocampal volume with increasing duration of depression results from a decrease in neurogenesis or altered gene expression (Sheline et al., 1996, Cobb et al., 2013). Methods Tissue punches from the dentate gyrus were collected from 23 subjects (MDD, medication-free) and 23 demographically-matched normal controls. Of the 23 subjects with MDD, 17 died by suicide and 17 had multiple depressive episodes. High quality total RNA, RNA Quality Index > 6, was isolated and whole transcriptome paired-end shotgun sequencing was performed using an Illumina NextSeq. 500. For each sample, raw RNA-seq reads (adapter-trimmed fastq files) were aligned to the Ensembl GRCh38 human reference genome using GSNAP (Genomic Short-read-Nucleotide Alignment Program). Differential gene expression was determined using cuffdiff, and core biological processes, molecular networks, and pathways pathologically disrupted in MDD were identified using Ingenuity Pathway Analysis. Results For each sample, 37 to 112 million reads were obtained and 64 to 96% were mapped successfully to the human genome, with most samples mapping above 85%. ‘Cuffdiff’ analysis in the Tuxedo suite revealed 30 significant genes differentially expressed in all MDD compared to controls (Lumenogix™, FDR Discussion The key finding in the primary MDD dataset as well as in the subsets is the overrepresentation of neuroinflammation related genes. Inflammatory and neurogenesis-related (ERK/MAPK) signaling pathways were significantly altered in the hippocampal dentate gyrus in MDD, with cytokine signaling and inflammatory pathways preferentially altered in MDD-suicide vs. MDD-non-suicide. Together this suggests that neuroinflammation, mediated by microglia and astrocytes may play a crucial role in major depressive disorder. These findings suggest a novel approach by seeking targets for new treatment of MDD that includes anti-inflammatory and neuroprotective properties.